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Search Results (1,178)

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15 pages, 3513 KB  
Article
Prevalence of Homologous Recombination Deficiency and Treatment Patterns in Patients with Newly Diagnosed Advanced Ovarian Cancer in Bulgaria: A Real-World Cohort Study (VALIDATE)
by Jeliazko Arabadjiev, Krasimir Nikolov, Marchela Koleva, Nikolay Shopov, Ivan Tonev, Rossitza Krasteva, Ivan Donev, Valeriy Yordanov, Velko Minchev and Assia Konsoulova
Medicina 2026, 62(5), 1000; https://doi.org/10.3390/medicina62051000 - 21 May 2026
Abstract
Background and Objectives: Although clinically useful, homologous recombination deficiency (HRD) testing has recently been more broadly adopted in ovarian cancer (OC) management. The VALIDATE study evaluated HRD status and treatment patterns in patients with newly diagnosed advanced OC in Bulgaria to better [...] Read more.
Background and Objectives: Although clinically useful, homologous recombination deficiency (HRD) testing has recently been more broadly adopted in ovarian cancer (OC) management. The VALIDATE study evaluated HRD status and treatment patterns in patients with newly diagnosed advanced OC in Bulgaria to better understand HRD prevalence and disease management. Materials and Methods: This real-world, observational, multi-centre, medical chart review study included 100 adult patients with HRD testing results available at study entry. Data collected at least 30 days after HRD results and 6 months later were descriptively analysed in the full cohort and subgroups (HRD, BRCA mutation, and genomic instability score [GIS]). Results: Mean age at diagnosis: 61.3 years; stage III: 51.0%, prevalence of HRD+ 58.0% (95% confidence intervals [CI] 47.7–67.8%) and HRD− 42.0% (95% CI 32.2–52.3%). Among the 58 HRD+ patients, 20 (34.5%) were BRCA+, whereas 38 (65.5%) were BRCA−, and 52 (89.7%) were GIS+, and 6 (10.3%) GIS−. Overall, platinum–taxane chemotherapy plus antiangiogenics was the most common front-line (FL) treatment (77.0%), regardless of subgroups (range: 66.7–85.0%). Six months later, 81 patients were alive, and 73 (90%) started maintenance therapy (MT). Antiangiogenic monotherapy (32.0%) and antiangiogenic plus PARP inhibitor (34.0%) were the most common MTs. The latter was also common across subgroups (range: 33.3–60.5%), except for HRD− (61.9% received antiangiogenic monotherapy). Conclusions: In this dataset, more than half of advanced OC patients had HRD+ status. Our study provides relevant insights into recent clinical practice patterns in advanced OC in Bulgaria that could serve as an anchor for future, more robust research in this field. Full article
(This article belongs to the Section Oncology)
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13 pages, 1123 KB  
Article
Morbidity, Recurrence and Survival Following Pelvic Exenteration for Gynaecological Malignancies: A Retrospective, Single-Centre Study
by Shruti Zalawadia, Sofia Lekka, Zahra Al-Jumaili, Elly Brockbank, Ranjit Manchanda, Arjun Jeyarajah, Saurabh Phadnis and Michail Sideris
J. Clin. Med. 2026, 15(10), 3957; https://doi.org/10.3390/jcm15103957 - 20 May 2026
Abstract
Background/Objectives: We evaluated perioperative morbidity, recurrence patterns and survival outcomes following pelvic exenteration (PE) at a tertiary referral centre. Methods: A retrospective observational study was conducted in women undergoing PE from 2004 to 2024. We collected demographics, performance status (PS), comorbidities, [...] Read more.
Background/Objectives: We evaluated perioperative morbidity, recurrence patterns and survival outcomes following pelvic exenteration (PE) at a tertiary referral centre. Methods: A retrospective observational study was conducted in women undergoing PE from 2004 to 2024. We collected demographics, performance status (PS), comorbidities, body mass index (BMI), tumour histology, intraoperative details, postoperative morbidity (Clavien–Dindo classification), mortality, length of stay (LOS), recurrence patterns and cancer-related death. Descriptive statistics were performed alongside Kaplan–Meier survival analysis. Results: Forty-seven patients underwent PE; median PS was 0 [interquartile range (IQR) 0–0]. Median ages at diagnosis and surgery were 55 (IQR 49–66) and 60 (IQR 50–68) years, respectively, with a median follow-up of 26 months (IQR 12–64). Thirty-two procedures (68%) were performed for recurrent and N = 15 (32%) for primary disease. Histology included N = 17 endometrial (36%), N = 10 vulval (23%), ovarian (15%), N = 5 cervical (11%) and N = 7 vaginal (15%) cases. Eighteen patients (38%) underwent total PE, N = 15 (32%) anterior PE and N = 14 (30%) posterior PE. Median blood loss was 1.5 L (IQR 0.85–2.0) and median operative time was 391 mis (IQR 313–482). Median HDU stay was 4 days (IQR 2–5) and LOS was 17 days (IQR 13–31). One postoperative death occurred. Major complications (Clavien–Dindo ≥3) occurred in 15 patients (32%). Late complications occurred in n = 17 (36.2%) women. Nineteen patients (41%) remained recurrence-free; N = 4 (9%) developed local and N = 24 (51%) distant recurrence. Mean overall survival time post-surgery for curative intent PE (N = 46) was 94 months (95%CI = 57–131 months); for primary tumours this was 51.6 (95%CI = 31–72) vs. 99 (56.01–142) for recurrent disease (p > 0.05). Conclusions: Pelvic exenteration is associated with acceptable morbidity and mortality in carefully selected patients, offering excellent locoregional disease control. Full article
(This article belongs to the Special Issue Clinical Application of Biomarkers in Cancers)
17 pages, 511 KB  
Article
Patients’ Perception of Follow-Up Care and Personal Health Status of 677 Long-Term Survivors of Gynecological Cancer from the Study “Expression IX—Long-Term Survival with Gynecological Cancer”: The International NOGGO, ENGOT and GCIG Survey
by Hannah Woopen, Tibor Zwimpfer, Luise Brenner, Clemens Liebrich, Katharina Leitner, Stephanie Henry, Cornelia Müller, Flurina Annacarina Maria Saner, Christoph Ebner, Desislava Dimitrova, Claudia Mang, Isabelle Himsl, Johanna Hell-Teutsch, Toon Van Gorp, Christian Braun, Yurtcu Nurhayat, Michael Müller, Lars Hanker, Viola Heinzelmann-Schwarz and Jalid Sehouli
Cancers 2026, 18(10), 1647; https://doi.org/10.3390/cancers18101647 - 20 May 2026
Abstract
Background: Long-term survivors (LTS) after gynecological cancer may be cured but still face physical and psychological challenges. This multicenter study aimed to assess the long-term side effects, the received follow-up care, and the personal perspectives of survivors. Methods: Between 2019 and 2025, LTS [...] Read more.
Background: Long-term survivors (LTS) after gynecological cancer may be cured but still face physical and psychological challenges. This multicenter study aimed to assess the long-term side effects, the received follow-up care, and the personal perspectives of survivors. Methods: Between 2019 and 2025, LTS from four European countries within the ENGOT (European Network of Gynecological Oncological Trial Groups) and GCIG (Gynecologic Cancer InterGroup) networks were recruited. Long-term survival was defined as surviving at least five years after the first diagnosis. LTS completed a questionnaire with 81 questions (patient’s characteristics, oncological history, current health status, lifestyle factors). Analyses were mainly descriptive. Results: A total of 677 LTS were enrolled, with a median age of 64.0 years (range: 26–92) and a median survival time of 7 years (range: 5–38). A total of 46.6% were diagnosed with cervical cancer, 32.9% with endometrial cancer, 4.4% with ovarian cancer, and 16.1% with other types of gynecological cancer. Moreover, 36.9% still suffer from physical and psychological symptoms, most frequently being lymphedema (36.2%), hot flashes (22.4%), difficulties with concentration (21.1%), fatigue (20.9%), vaginal dryness (20.1%), and urinary incontinence (18.9%). Median overall health status was ranked (scale 1–5; 1 = very good, 5 = very poor) as 2, while 13.5% rated their health as poor/very poor. Current symptoms were associated with poorer health status (p < 0.001) and a history of recurrent disease (p = 0.001). In addition, 13.6% reported not receiving follow-up care. CA-125 was determined in 80.8% of ovarian LTS, as well as in 30.7% of cervical and 28.9% of endometrial LTS. Pap smear follow-up was reported by 50.5% of endometrial LTS. A total of 33.7% did not exercise at all or exercised less than an hour per week, 13.4% smoke tobacco, and 51.2% drink alcohol more often than once a month. Conclusions: Our findings highlight the need for patient-centered follow-up care, addressing both long-term side effects and education on lifestyle and prevention. Follow-up procedures that do not follow guidelines should be avoided. Full article
(This article belongs to the Special Issue Patients’ Perspective in Gynecological Cancer)
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33 pages, 777 KB  
Review
cGAS-STING Signaling as a Molecular Bridge Between Inflammation, Ovarian Ageing, and Reproductive Failure
by Charalampos Voros, Fotios Chatzinikolaou, Georgios Papadimas, Ali Can Gunes, Aristotelis-Marios Koulakmanidis, Ioannis Papapanagiotou, Athanasios Karpouzos, Diamantis Athanasiou, Kyriakos Bananis, Antonia Athanasiou, Aikaterini Athanasiou, Charalampos Tsimpoukelis, Maria Anastasia Daskalaki, Christina Trakatelli, Nikolaos Thomakos, Panagiotis Antsaklis, Dimitrios Loutradis and Georgios Daskalakis
Int. J. Mol. Sci. 2026, 27(10), 4559; https://doi.org/10.3390/ijms27104559 - 19 May 2026
Viewed by 217
Abstract
Infertility and ovarian ageing are increasingly acknowledged as illnesses affected not just by endocrine decline but also by chronic inflammatory stress and mitochondrial dysfunction in the reproductive milieu. The cGAS-STING signalling pathway has emerged as a significant possibility linking these activities. The cGAS-STING [...] Read more.
Infertility and ovarian ageing are increasingly acknowledged as illnesses affected not just by endocrine decline but also by chronic inflammatory stress and mitochondrial dysfunction in the reproductive milieu. The cGAS-STING signalling pathway has emerged as a significant possibility linking these activities. The cGAS-STING pathway, originally defined as a cytosolic DNA-sensing mechanism essential for innate immune defence, is now recognised as a broader modulator of sterile inflammation, cellular senescence, and tissue failure. Experimental reproductive models suggest that the activation of this system may operate as a crucial link between mitochondrial dysfunction, cytosolic DNA accumulation, inflammatory cytokine production, and the progressive decline of ovarian and endometrial function. The activation of cGAS-STING in granulosa cells has been associated with inflammatory signalling and impaired steroidogenic activity. Full article
(This article belongs to the Collection Advances in Cell and Molecular Biology)
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15 pages, 701 KB  
Article
ADHD and Binge Eating Symptoms in Adult Women: A Cross-Sectional Study with a Gender-Focused Theoretical Overview
by Edoardo Mocini, Alessia Maiolo, Valerio Riccardo Aquila, Maria Eugenia Caligiuri, Francesca Greco, Gian Pietro Emerenziani, Emanuele Tinelli, Umberto Sabatini, Elisa Giannetta and Maria Grazia Tarsitano
Women 2026, 6(2), 34; https://doi.org/10.3390/women6020034 - 19 May 2026
Viewed by 116
Abstract
Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition frequently associated with psychiatric comorbidity, including disordered eating. Adult women remain under-recognized and underrepresented in ADHD research, and emerging evidence suggests that symptom expression may be shaped by gendered social factors, ovarian hormone fluctuations, and [...] Read more.
Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition frequently associated with psychiatric comorbidity, including disordered eating. Adult women remain under-recognized and underrepresented in ADHD research, and emerging evidence suggests that symptom expression may be shaped by gendered social factors, ovarian hormone fluctuations, and metabolic health. In this manuscript, we provide a gender-focused theoretical overview of the literature linking ADHD to binge eating symptoms in adult women, with attention to underdiagnosis, menstrual cycle-related symptom variability, and obesity-related metabolic risk, and empirically test the association between a self-reported ADHD diagnosis and binge eating symptoms in an online cross-sectional sample of adult women. Women reporting an ADHD diagnosis (n = 140) were compared with a random subsample of n = 140 women without ADHD drawn from the same survey; comparability between groups on age, education, and employment was formally verified; and binge eating symptoms were assessed with the Binge Eating Scale (BES) as a continuous outcome and as an ordered three-category variable. Women reporting an ADHD diagnosis showed significantly higher BES scores than controls (rank-biserial r = 0.28, 95% CI 0.15–0.41), and a higher proportion of severe binge eating symptomatology (BES ≥ 27; 22.1% vs. 11.4%; OR = 2.20, 95% CI 1.14–4.25) than controls. The association remained significant in a sensitivity analysis adjusting for age and BMI. Taken together, our findings support the need for routine, gender-sensitive screening for binge eating symptoms in women with ADHD, as well as ADHD screening in women presenting with binge eating and obesity. Full article
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13 pages, 1954 KB  
Article
Dietary Supplementation with Raspberry or Strawberry Seed Oil Impacts Folliculogenesis, Hormonal Parameters and the Fatty Acid Profile in the Juvenile Rabbit Ovary
by Małgorzata Grzesiak, Katarzyna Michta, Kalina Galińska, Michał Kmiecik and Sylwia Pałka
Animals 2026, 16(10), 1528; https://doi.org/10.3390/ani16101528 - 16 May 2026
Viewed by 177
Abstract
This study demonstrated the effects of dietary supplementation with 1% raspberry (RO) or 1% strawberry (SO) seed oil from 5 to 12 weeks of age (n = 6/group) on folliculogenesis, hormonal parameters, the ovarian fatty acid profile, and the expression of related [...] Read more.
This study demonstrated the effects of dietary supplementation with 1% raspberry (RO) or 1% strawberry (SO) seed oil from 5 to 12 weeks of age (n = 6/group) on folliculogenesis, hormonal parameters, the ovarian fatty acid profile, and the expression of related genes in juvenile rabbits. After slaughter, ovaries and blood were collected. Ovaries were used for histology, fatty acid profiling, and gene expression analysis, while plasma was used to measure progesterone (P4), testosterone (T), estradiol-17β (E2), follicle-stimulating hormone (FSH), and anti-Müllerian hormone (AMH) concentrations. Both RO and SO reduced the number of primary follicles (p = 0.04), whereas RO increased the number of antral follicles (p = 0.04) compared with the control. In both supplemented groups, FSH (p = 0.04 and p = 0.035) and AMH (p = 0.04) concentrations were higher. RO increased P4 and E2 (p = 0.03 and p = 0.013) concentrations, while SO only increased P4 (p = 0.02) levels. SO altered the ovarian fatty acid profile, increasing selected monounsaturated fatty acids and reducing polyunsaturated fatty acids, likely by increasing the expression of the converting enzyme, stearoyl-CoA desaturase 5 (p = 0.038). Overall, both oils influenced folliculogenesis through hormonal changes, and SO modified ovarian fatty acid composition, which may affect ovarian function in juvenile rabbits. Full article
(This article belongs to the Section Animal Reproduction)
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21 pages, 374 KB  
Review
Beyond Survival: Integrating Fertility Preservation into Gynaecologic Cancer Management
by Christina Pappa, Muhammad Fatum, Haya Nasser, Umniah Khajori, Danielle Christmas, Nouf Khalifeh, Mohammad Daas and Moiad Alazzam
Reprod. Med. 2026, 7(2), 22; https://doi.org/10.3390/reprodmed7020022 - 13 May 2026
Viewed by 333
Abstract
As survival rates among patients with gynaecological cancers continue to improve, fertility preservation has become an increasingly important aspect of comprehensive cancer care, particularly for younger women diagnosed during their reproductive years. The impact of treatment on fertility varies according to cancer type, [...] Read more.
As survival rates among patients with gynaecological cancers continue to improve, fertility preservation has become an increasingly important aspect of comprehensive cancer care, particularly for younger women diagnosed during their reproductive years. The impact of treatment on fertility varies according to cancer type, stage, and modality, necessitating individualised preservation strategies. Fertility preservation is both feasible and safe in carefully selected patients with early-stage gynaecological cancers. Oocyte and embryo cryopreservation remain the most widely accepted techniques, particularly when time allows for ovarian stimulation. Fertility-sparing surgeries, such as radical trachelectomy and conservative management of early endometrial cancer, have shown promising oncological and reproductive outcomes. However, barriers including access, timing, and awareness continue to limit broader implementation. In modern society, fertility-preserving strategies should form an integral part of treatment planning for reproductive-aged women with gynaecological malignancies. Early referral to a fertility specialist, patient-centred counselling, and a coordinated multidisciplinary approach are essential to optimise both oncological and reproductive outcomes. Further research and education are required to refine guidelines and expand access to fertility-preserving care. This review presents the current fertility preservation options available to women with gynaecological cancers, including cervical, ovarian, and endometrial malignancies, and highlights the importance of early multidisciplinary intervention in delivering personalised care. Full article
16 pages, 585 KB  
Article
Genetic Variations in the Fibronectin 1 Gene (FN1) and Risk of Female Reproductive Cancers—A Preliminary Study
by Piotr Pawlik, Grażyna Kurzawińska, Marcin Ożarowski, Tomasz M. Karpiński, Anna Bogacz, Piotr J. Olbromski, Aleksandra E. Mrozikiewicz, Maciej Brązert, Wiesław Markwitz and Agnieszka Seremak-Mrozikiewicz
Int. J. Mol. Sci. 2026, 27(10), 4302; https://doi.org/10.3390/ijms27104302 - 12 May 2026
Viewed by 210
Abstract
We investigated five single-nucleotide variants (SNVs) of the FN1 gene in female reproductive organ cancers. The proteins expressed by this gene are essential components of the extracellular matrix (ECM) that constitutes the tumor microenvironment (TME). The study group included 208 women diagnosed with [...] Read more.
We investigated five single-nucleotide variants (SNVs) of the FN1 gene in female reproductive organ cancers. The proteins expressed by this gene are essential components of the extracellular matrix (ECM) that constitutes the tumor microenvironment (TME). The study group included 208 women diagnosed with cervical, uterine, and ovarian cancers and 208 age-matched cancer-free controls. Genomic DNA from whole blood was used to analyze five intronic SNVs of the FN1 gene using PCR/RFLP. The results indicate that two of the studied FN1 gene variants may increase the risk of gynecological cancers in dominant and log-additive models (p = 0.048 and p = 0.040 for rs6725958, p = 0.033 and p = 0.038 for rs1968510, respectively). Comparing individual cancer groups with the controls, differences were observed for the ovarian cancer group (rs1968510 p = 0.015 and p = 0.016, rs6725958 p = 0.070 and p = 0.037 in dominant and log-additive models, respectively). None of these associations remained statistically significant after Bonferroni correction for multiple testing. Haplotype analyses revealed that the AGATC haplotype, containing minor alleles for rs35343655 and rs6725958, was more frequent in the entire gynecological cancer group (p = 0.0036). For individual cancer types, values of p = 0.0071 for ovarian, p = 0.0028 for endometrial, and p = 0.0269 for cervical cancers were obtained; Our preliminary study suggests that the rs6725958 and rs1968510 FN1 variants may slightly increase the risk of female reproductive system cancers, particularly ovarian cancer. These findings require further validation in larger, independent cohorts and functional studies. Full article
(This article belongs to the Section Molecular Oncology)
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35 pages, 23356 KB  
Article
Gut-Derived Lipid Mediators Orchestrate Ovarian Metabolic Homeostasis and Clutch Persistence in Aging Laying Hens via the PLA2G6-ALOX15B-AGPAT3 Axis
by Xin Li, Xiaoliang Wang, Xia Cai, Qiang Meng, Yanyan Sun, Changsuo Yang and Junfeng Yao
Biomolecules 2026, 16(5), 708; https://doi.org/10.3390/biom16050708 - 11 May 2026
Viewed by 260
Abstract
Clutch persistence, defined as the ability to sustain consecutive egg-laying cycles, is a pivotal determinant of profitability in the poultry industry, particularly for aging laying hens (≥65 weeks). However, the molecular mechanisms governing this trait remain elusive, largely due to the traditional “ovary-centric” [...] Read more.
Clutch persistence, defined as the ability to sustain consecutive egg-laying cycles, is a pivotal determinant of profitability in the poultry industry, particularly for aging laying hens (≥65 weeks). However, the molecular mechanisms governing this trait remain elusive, largely due to the traditional “ovary-centric” paradigm that overlooks systemic regulation by the gut microbiota. To address this knowledge gap, the present study aimed to dissect the comprehensive regulatory network governing clutch persistence using integrated multi-omics analyses. A total of 20 sixty-five-week-old Rhode Island Red (RIR) laying hens with cumulative egg production exceeding 300 eggs but distinct clutch persistence were stratified into a high-clutch persistence group (HCP, ≥25 clutches, n = 10) and a low-clutch persistence group (LCPLCP, ≤15 clutches, n = 10). Multi-omics profiling, including ovarian transcriptomics, proteomics, and metabolomics; serum metabolomics; and cecal microbiota 16S rRNA sequencing was performed. Data integration and association mining were conducted via Spearman correlation analysis with stringent thresholds (r > 0.6, p < 0.01). Integrated analyses revealed a “gut–ovary axis” regulatory model mediated by a lipid mediator network, operating through a three-tiered mechanism: (1) Gut Initiation: The HCP group exhibited enriched cecal γ-Proteobacteria, which promoted biosynthesis of lipid precursors. (2) Serum Transport: Key serum lipid mediators, most notably LysoPC (22:6) (VIP = 4.5) and cholesterol ester CE (20:4), served as critical carriers transducing gut-derived signals to the ovary. (3) Ovarian Execution: These lipid signals activated a core ovarian metabolic pathway centered on the PLA2G6-ALOX15B-AGPAT3 axis, which coordinated follicular development and ovulation by supplying steroid hormone synthesis substrates, exerting anti-inflammatory effects, and stabilizing membrane structures. Collectively, this study demonstrates that gut microbiota modulates clutch persistence in aging laying hens via lipid mediators, orchestrating a systemic “gut–serum–ovary” regulatory cascade. These findings provide a novel molecular framework for extending the economic egg-laying cycle through the targeted manipulation of intestinal microbiota or serum lipid metabolism. Full article
(This article belongs to the Section Lipids)
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20 pages, 16001 KB  
Article
Establishment of an Autoimmune Premature Ovarian Insufficiency Mouse Model with Proteomic Analyses: An Exploratory Study
by Ying Tian, Jiaqi Zhou, Xinyi Pei, Feiran Liu and Feiyang Diao
Int. J. Mol. Sci. 2026, 27(10), 4270; https://doi.org/10.3390/ijms27104270 - 11 May 2026
Viewed by 349
Abstract
Premature ovarian insufficiency (POI) impairs fertility and health in reproductive-age women, with autoimmune factors contributing to 4–30% of cases. To investigate immune dysregulation in POI, we developed two mouse models using pZP3 induction: regular immune (RE-POI) and enhanced immune (EN-POI) cycles. The EN-POI [...] Read more.
Premature ovarian insufficiency (POI) impairs fertility and health in reproductive-age women, with autoimmune factors contributing to 4–30% of cases. To investigate immune dysregulation in POI, we developed two mouse models using pZP3 induction: regular immune (RE-POI) and enhanced immune (EN-POI) cycles. The EN-POI model exhibited stable, irreversible ovarian dysfunction, including disrupted estrous cycles, hormonal changes (elevated FSH, decreased AMH, and estradiol), follicular depletion, and infertility. Immune profiling demonstrated consistent T-lymphocyte imbalance across both RE-POI and EN-POI model groups, characterized by expanded splenic CD4+ T cells, diminished regulatory T cells, elevated systemic inflammatory cytokines, and ovarian fibrosis. Proteomic comparison between the control and EN-POI groups identified 198 differentially expressed proteins, mainly enriched in immune and inflammatory pathways. Based on these differential proteins, subsequent network analysis further identified six key hub proteins, namely Mmp9, Isg15, Ikbke, Siglec1, Pf4, and Cdkn1b. This study establishes a stable autoimmune POI model, elucidates T-cell imbalance with cytokine storm and fibrosis, and identifies key molecules linking immune abnormalities to ovarian failure, offering new insights into POI research. Full article
(This article belongs to the Section Molecular Immunology)
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17 pages, 588 KB  
Article
Assessment of Maropitant Citrate Effectiveness as an Intraoperative Analgesic Through Monitoring Parasympathetic Tone Activity in Female Dogs Undergoing Ovariohysterectomy
by Areli Ramírez-Castillo, Claudia Interlandi, Agatha Elisa Miranda Cortés, Navid Ziaei-Darounkolaei, Alejandro Casas-Alvarado, Alejandro Jiménez-Yedra and Ismael Hernández-Avalos
Vet. Sci. 2026, 13(5), 463; https://doi.org/10.3390/vetsci13050463 - 10 May 2026
Viewed by 911
Abstract
Maropitant has been proposed as an adjunct for pain relief in dogs undergoing surgeries like ovariohysterectomy (OVH), but its effectiveness has not yet been definitively proven. This study aimed to assess the intraoperative analgesic effect of intravenously administered maropitant citrate at a constant [...] Read more.
Maropitant has been proposed as an adjunct for pain relief in dogs undergoing surgeries like ovariohysterectomy (OVH), but its effectiveness has not yet been definitively proven. This study aimed to assess the intraoperative analgesic effect of intravenously administered maropitant citrate at a constant rate infusion through monitoring parasympathetic tone activity in female dogs undergoing OVH. Thirty healthy females of various breeds, with an average age of 3.8 ± 2.7 years, an average weight of 16.75 ± 10.68 kg, were randomly assigned to two treatment groups. The group receiving maropitant (GMaro, n = 15) was given a 1 mg kg−1 maropitant bolus intravenously (IV), followed by a continuous infusion of 100 mcg kg−1 min−1. The lidocaine group (GLido, n = 15) received a 2 mg/kg lidocaine IV bolus, with subsequent infusion at 50 mcg kg−1 min−1. Cardiorespiratory variables and the PTA index were evaluated at 11 anesthetic time points. Overall, cardiovascular variables such as Heart Rate (HR) and systolic arterial pressure (SAP) significantly decreased during anesthesia induction in the GMaro (p = 0.0001; p = 0.01, respectively) and in GLido (p = 0.01). Differences between groups during induction were observed in HR (p = 0.03), SAP (p = 0.04), and mean arterial pressure (MAP) (p = 0.03). MAP showed significant changes from baseline at the start of surgery and during clamping in both GMaro (p = 0.03) and GLido (p = 0.003). Regarding ventilatory variables—pulse oximetry (SpO2), respiratory rate (RR), inspired oxygen fraction (FiO2), end-tidal CO2 (EtCO2)—no group differences were found, but RR (GMaro; p = 0.001, GLido; p = 0.0001) and SpO2 (GMaro; p = 0.004, GLido; p = 0.04) differed significantly from baseline due to the controlled clinical setting. During anesthesia maintenance, end-tidal isoflurane (ETIso) increased significantly in the GLido (p = 0.009), with no difference between groups (p = 0.94). Finally, only the PTA energy variable showed a significant decrease in the GMaro (p = 0.0006), and a significant difference in this parameter was observed during right ovarian pedicle manipulation between groups (p = 0.02). In conclusion, continuous intravenous infusion of maropitant citrate at 100 mcg kg−1 h−1 effectively reduced the sympathetic response related to nociception, similar to lidocaine, in healthy female dogs undergoing OVH. Full article
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23 pages, 2185 KB  
Article
Germline Genetic Testing in Breast and Gynecologic Cancers: Evaluating Age at Diagnosis as a Determinant
by Eirini Papadopoulou, Georgios N. Tsaousis, Romina Alevizou, Dimitrios Alexandrou, Theodoros Argyriou, Anna Giannopoulou, Markos Thanos, Sofia Kakoulaki, Christos Kalyvopoulos, Maria Kanara, Christos Kanistras, Nikolaos Katsiakis, Anastasios Katsourakis, Dimitrios Kokkonis, Theodoros Kontoulis, Ioanna Konstantiadou, Dimitrios Tryfonopoulos, Sofia Karageorgopoulou, Anna Koumarianou, Dimitrios Ziogas, Stavros Bikos, Effrosyni Bompou, Georgios Boutsikos, Varvara Pantelidou, Aikaterini Savvidou, Vasileios Sakellariou, Maria Matiatou, Panagiotis Karathanasis, Maroulio Stathoulopoulou and Vassileios Venizelosadd Show full author list remove Hide full author list
Cancers 2026, 18(10), 1541; https://doi.org/10.3390/cancers18101541 - 10 May 2026
Viewed by 361
Abstract
Background: Breast cancer and gynecological malignancies, including cervical, ovarian, and endometrial cancers, remain leading causes of cancer incidence and mortality among women worldwide. This study investigated hereditary predisposition rates in women diagnosed with breast or gynecological cancer, focusing on the effect of age [...] Read more.
Background: Breast cancer and gynecological malignancies, including cervical, ovarian, and endometrial cancers, remain leading causes of cancer incidence and mortality among women worldwide. This study investigated hereditary predisposition rates in women diagnosed with breast or gynecological cancer, focusing on the effect of age on germline pathogenic/likely pathogenic (P/LP) variant detection. We sought to determine whether younger age at diagnosis should be used as a criterion for patient selection for genetic testing. Methods: A total of 9084 consecutive females with breast cancer or gynecological tumors underwent germline NGS-based genetic testing (52 cancer-relevant genes) at Genekor laboratory from 2020–2026. Multivariable logistic regression evaluated factors associated with P/LP variant detection, adjusting for tumor type and family history. Results: Overall P/LP prevalence was approximately 20% (one in five patients), with tumor-specific rates of 19.24% in breast cancer, 27.59% in ovarian cancer, and 26.67% in endometrial cancer. P/LP prevalence declined significantly with age from 24.37% in patients <40 years to 15.90% in those ≥70 years, while Variants of Uncertain Significance (VUS) remained stable (40–43%). P/LP patients had earlier diagnosis (median 45 vs. 46 years, p < 0.001), driven predominantly by high-risk genes (13.87% in <40 y vs. 7.11% in ≥70 y). BRCA1 showed stronger age enrichment than BRCA2 (8.14% vs. 3.16% in <40 y; median diagnosis 43 vs. 45 years). Age remained independently associated with P/LP detection in multivariable analysis, with an 18% reduction in odds per 10-year increase for any P/LP (OR 0.82, 95% CI 0.78–0.86) and a stronger 28% reduction for high-risk variants (OR 0.72, 95% CI 0.67–0.78). Family history also independently predicted P/LP detection (OR 1.40, 95% CI 1.19–1.66). Conclusions: Although derived from a referral-based (and thus selected) population, these findings show that while younger patients have a higher prevalence of high-risk P/LP variants, clinically actionable findings are present across all age groups, including those ≥70 years. These results suggest that reliance on age alone to determine eligibility for genetic testing may be insufficient. Broadening access to testing beyond strict age-based criteria could improve the identification of hereditary cancer risk and inform patient management, although further evaluation in less selected populations is warranted. Full article
(This article belongs to the Section Molecular Cancer Biology)
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20 pages, 1524 KB  
Article
Comparing the Effects of Glyphosate and Mycotoxins in the Human Follicular Microenvironment: An Exploratory Exposome Study
by Apolka Szentirmay, Márkó Unicsovics, Eszter Ruff, Bernadett Csókay, Katalin Sára-Popovics, Dóra Holéci, Tímea Buzder, Miklós Sipos, Attila Martonos, Attila Sajgó, Natália Szeőcs, György Nagyéri, Levente Sára and Zsuzsanna Szőke
Biomedicines 2026, 14(5), 1081; https://doi.org/10.3390/biomedicines14051081 - 9 May 2026
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Abstract
Background: Exposure to anthropogenic and/or natural (e.g., herbicides or mycotoxins) endocrine-disrupting chemicals (EDCs) has been linked to several reproductive disorders. Glyphosate (GLY), a common agricultural agent, is a potential element of the exposome that bioaccumulates and has potential endocrine and oxidative stress-related [...] Read more.
Background: Exposure to anthropogenic and/or natural (e.g., herbicides or mycotoxins) endocrine-disrupting chemicals (EDCs) has been linked to several reproductive disorders. Glyphosate (GLY), a common agricultural agent, is a potential element of the exposome that bioaccumulates and has potential endocrine and oxidative stress-related effects. However, data on its presence in the human ovarian microenvironment remain limited. Our study examined GLY levels in follicular fluid (ff) and serum and their relationships with oxidative stress markers, reproductive hormones, and stress hormones in women undergoing in vitro fertilization (IVF). Methods: 50 women undergoing controlled ovarian stimulation participated. Serum and ff samples were routinely collected during oocyte retrieval. GLY, related hormones (e.g., cortisol, estradiol-E2, anti-Müllerian hormone-AMH, and melatonin-MT), an oxidative stress marker malondialdehyde (MDA), antioxidant enzyme activities, total antioxidant capacity, and co-occurring natural pollutant mycotoxin levels were measured. Relationships between GLY levels and these mediators were assessed using correlation and regression analyses. Results: GLY was detected in both serum and ff at similar concentrations (0.038 ± 0.006 ng/mL vs. 0.045 ± 0.006 ng/mL; p = 0.414). Follicular GLY levels showed a positive association with MDA (Spearman’s r = 0.4487, p < 0.001), explaining 28.6% of the variability in follicular MDA. Serum GLY was positively associated with serum (β = 40.26, p = 0.0058) and follicular E2 (r = 0.29, p = 0.042). Serum GLY levels were negatively correlated with cortisol (β = −0.0188, p = 0.020). A slight correlation between follicular GLY and MT was observed (p = 0.03). No associations were found between GLY levels and age, body mass index, AMH, the recombinant gonadotropin dose used, antioxidant enzyme activities, follicle count, oocyte yield, or embryo viability. Conclusions: This study might be the first to demonstrate the presence of GLY of exposome in human ff, indicating that environmental exposure to GLY may reach the oocyte microenvironment. The correlation with lipid peroxidation suggests GLY could contribute to follicular oxidative stress. The associations with E2 and cortisol point to potential endocrine-disrupting effects. While no direct impact on IVF outcomes was observed, findings suggest low-level exposure to GLY could influence ovarian physiology through specific biochemical mechanisms. Full article
(This article belongs to the Section Drug Discovery, Development and Delivery)
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25 pages, 27894 KB  
Article
Fisetin Attenuates D-Gal-Induced Ovarian Aging by Modulating Mitophagy via the AMPK/mTOR Pathway
by Juan Dong, Yaxin Zhu, Zongyang Li, Yanyan Chang, Xiyuan Yan, Caiqiao Zhang and Dong Niu
Antioxidants 2026, 15(5), 602; https://doi.org/10.3390/antiox15050602 - 9 May 2026
Viewed by 391
Abstract
This study aimed to explore the alleviating effects of fisetin, a polyphenolic flavonoid, on ovarian dysfunction in a D-galactose (D-gal)-induced aging mouse model, as well as the underlying mechanisms, using both in vivo and in vitro experiments. Mice were subcutaneously injected with D-gal [...] Read more.
This study aimed to explore the alleviating effects of fisetin, a polyphenolic flavonoid, on ovarian dysfunction in a D-galactose (D-gal)-induced aging mouse model, as well as the underlying mechanisms, using both in vivo and in vitro experiments. Mice were subcutaneously injected with D-gal (100 mg/kg/day) for 60 days to establish the ovarian aging model; during the final 30 days, fisetin (10, 20, 30 mg/kg/day) was given orally. In addition, a senescent model of granulosa cell (GC) was established using D-gal and treated with fisetin. Fisetin supplementation improved ovarian endocrine function and reproductive capacity in aging mice, as reflected by regularized estrous cycles, elevated estradiol levels, and increased embryo numbers. Furthermore, fisetin reduced the number of atretic follicles and the extent of ovarian fibrosis and senescence, while simultaneously restoring the proliferation-apoptosis balance in follicular GCs, as well as alleviating oxidative stress. RNA-sequencing revealed that AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR) signaling and mitophagy were involved in the protective effects of fisetin against ovarian aging. Consistently, fisetin treatment promoted mitophagy, accompanied by AMPK/mTOR activation in ovarian tissues and GCs following D-gal exposure. Inhibition of AMPK attenuated the effect of fisetin on mitophagy. Additionally, blockage of mitophagy also reversed the beneficial effects of fisetin on mitochondrial injury, oxidative stress, cell cycle arrest, and cellular senescence in D-gal-induced senescent GCs. These findings indicate that fisetin prevents ovarian aging by suppressing follicular GC oxidative damage and ameliorating cell cycle arrest via activation of AMPK/mTOR-mediated mitophagy, thereby preserving female fertility. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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16 pages, 769 KB  
Review
East–West Disparities in Lung Cancer Screening: Subsolid Nodule Prevalence, Interval Growth, and Decision-Making Analysis
by Yi-Chi Hung, Yun-Ju Wu and Fu-Zong Wu
Diagnostics 2026, 16(10), 1442; https://doi.org/10.3390/diagnostics16101442 - 8 May 2026
Viewed by 218
Abstract
Lung cancer screening has been widely studied, and strong evidence supports its role in reducing mortality among heavy smokers. The 2011 National Lung Screening Trial demonstrated a 20% reduction in lung cancer mortality, with further validation from European trials, such as NELSON and [...] Read more.
Lung cancer screening has been widely studied, and strong evidence supports its role in reducing mortality among heavy smokers. The 2011 National Lung Screening Trial demonstrated a 20% reduction in lung cancer mortality, with further validation from European trials, such as NELSON and MILD. In 2015, the United States Centers for Medicare & Medicaid Services approved lung cancer screening as a reimbursable service, later expanding the criteria in 2021 to include individuals aged 50–80 years with a ≥20 pack-year smoking history. While screening models such as the Prostate, Lung, Colorectal, and Ovarian (PLCO) have effectively stratified risk among smokers, emerging research on non-smokers remains inconclusive. This review highlights five key issues in lung cancer screening in Eastern and Western countries. First, the screening rates differ significantly between regions owing to variations in healthcare policies and awareness. Second, subsolid nodule (SSN) prevalence varies between Eastern and Western populations, influencing screening strategies. Third, differences in SSN growth thresholds affect clinical decision-making and patient outcomes. Fourth, there are variations in the management of SSNs, particularly in follow-up recommendations and intervention strategies. Fifth, overdiagnosis remains a critical concern, with distinct challenges in each region owing to screening frequency and healthcare infrastructure. Additionally, microsimulation models predict a decline in smoking-related lung cancer but an increase in non-smoking-related cases, emphasizing the need for tailored screening approaches. Addressing these five issues is crucial for optimizing lung cancer screening strategies and balancing early detection with the risk of overdiagnosis. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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