Abstract Background Abnormal syncytialization of cytotrophoblast (CTB) cells is known to be associated with preeclampsia (PE), however, the underlying molecular mechanisms remain elusive. Results In this study, proteomic analysis of placental tissues was performed to identify proteins involved in PE pathogenesis. NCK Adaptor Protein 1 (NCK1) was found to be downregulated in placental tissues from patients with early-onset PE. In vitro functional assays revealed that NCK1 was markedly increased during spontaneous syncytialization of CTB cells. NCK1 overexpression alleviated hypoxia-induced defects in CTB cell fusion. Mechanistically, NCK1 upregulated both the expression and stability of Peroxisome Proliferator-Activated Receptor Gamma (PPARG), accompanied by increased m6A modification of its mRNA. Overexpression of PPARG significantly rescued hypoxia-induced syncytialization impairment, whereas PPARG deficiency abolished the promotive effects of NCK1 on CTB syncytialization. Additionally, phosphorylation of Eukaryotic Translation Initiation Factor 3 Subunit (EIF3D) was significantly increased during spontaneous syncytialization, and NCK1 overexpression partially reversed hypoxia-induced suppression of EIF3D phosphorylation. EIF3D knockdown significantly reduced m6A levels on PPARG mRNA, likely due to impaired NCK1-mediated suppression of Alpha-Ketoglutarate-Dependent Homolog 5 (ALKBH5), an m6A demethylase. Furthermore, NCK1 enhanced EIF3D phosphorylation by inhibiting its O-GlcNAcylation. Conclusions Our findings demonstrate that NCK1 stabilizes PPARG by modulating the crosstalk between O-GlcNAcylation and phosphorylation of EIF3D, thereby restoring hypoxia-impaired syncytialization in CTB cells. This study identifies the NCK1/EIF3D/PPARG axis as a molecular pathway potentially relevant to trophoblast fusion dysfunction in PE.

Osteosarcoma (OS) is a primary bone malignancy, and its progression can be hindered by inducing programmed cell death (PCD). Protein disulfide-isomerase (PDI) regulates cancer cell death; however, its functional role in OS remains unclear. P4HB expression was assessed in tumor tissues and cells from patients with OS using RT-qPCR. The effects of P4HB on OS cell lines were evaluated. Western blotting was used to assess the impact of P4HB on various forms of PCD (apoptosis, ferroptosis, and pyroptosis). Bioinformatics analysis identified the upstream and downstream mechanisms of P4HB in OS progression. A xenograft tumorigenesis study was performed to elucidate the role and mechanism of P4HB in OS progression. Elevated P4HB expression was observed in OS tissue samples and cell lines. Downregulation of P4HB suppressed OS cell growth, migration, and invasiveness and induced PCD. Functional enrichment analysis and experimental validation revealed that PDI upregulated vascular endothelial growth factor A (VEGFA) vascular endothelial growth factor receptor 2 (VEGFR2) signaling. Methylation analysis showed that the m6A demethylase fat mass and obesity-associated protein (FTO) decreased P4HB m6A levels and enhanced VEGFA-VEGFR2 signaling in OS cells. Moreover, FTO overexpression enhanced the proliferative, migratory, and invasive capabilities of OS cells and decreased PCD. Finally, FTO knockdown inhibited tumor growth and lung metastasis of OS by decreasing the activity of the PDI/VEGFA-VEGFR2 signaling axis. Mechanistically, FTO-mediated m6A modification of P4HB regulates PCD in OS through activation of this axis. © 2026 The Pathological Society of Great Britain and Ireland.

Gynecological infections and implant-related complications, such as bacterial vaginosis (BV), pelvic inflammatory disease (PID), and endometritis, are exacerbated by biofilm-forming pathogens such as G. vaginalis, E. coli, and S. aureus, posing significant clinical challenges worldwide. These biofilms, resistant to antibiotics, contribute to chronic infections and device failures in gynecological implants. Rising antibiotic resistance underscores the need for innovative biomaterials. Chitosan, hyaluronic acid (HA) and alginate are three representative natural polysaccharides, showing broad application potential in antibacterial materials and tissue engineering due to their excellent biocompatibility, biodegradability and modifiable structures. In their natural forms, they exhibit a certain degree of anti-biofilm activity by inhibiting bacterial adhesion and disrupting bacterial membranes. Functional modification significantly enhances their antibacterial performance such as AMPs grafting, cross-linking, quaternization, and nanocomposites. This review explores the antibacterial mechanisms of natural polysaccharides in the vaginal microbiome and endometrial tissue, highlighting advances in functionalization with antimicrobial peptides, nanoparticles, and chemical modifications to enhance antibacterial efficacy. The toxicological effects of natural polysaccharide materials on gynecological tissues generally show the characteristics of mainly protective and restorative effects, rather than causing damage. Natural polysaccharides and their applications offer promising potential for infection-resistant, regenerative therapies in gynecology, promising safer and more effective interventions.

Cancer is a major global public health challenge. Traditional treatments such as surgery, radiotherapy, and chemotherapy often show limited efficacy, minimal improvements in survival rates, and high recurrence risks. With limited therapeutic options for solid tumors, tumor immunotherapy, which harness the body's immune system, has gained significant attention. Oncolytic viruses (OVs) selectively infect and destroy tumor cells, induce immunogenic cell death (ICD) and stimulate antitumor immune responses. However, current OVs therapies, which are predominantly administered via intratumoral injection, have numerous limitations, including the need for guidance, suboptimal viral spread, extracellular matrix barriers, and immune clearance. These challenges hinder repeated dosing effectiveness and restrict its clinical applicability. Although genetic engineering has improved the tumor selectivity and immune activation of OVs, significant delivery challenges remain. Recently, optimizing pharmaceutical formulations to enhance tumor targeting and viral accumulation has emerged as a key approach to improving OV therapy and expanding clinical applicability. This review highlights the critical role of pharmaceutical formulations in biologics and outlines recent advances in OVs formulations. Specifically, we discuss strategies aimed at enhancing tumor targeting, reducing adverse effects, and promoting antitumor immunity. These strategies significantly enhance OV therapeutic potential and inform novel delivery systems for clinical translation.

The study investigates the therapeutic potential of enzyme variations EP-22, DS-13, and SM-47 in cervical cancer treatment using HeLa and SiHa cell lines, focusing on their effects on cell viability, migration, and molecular targets. The MTT assay findings also show that at a concentration of 50 mu g/mL, EP-22 has an IC50 value of 35 % for HeLa cells and 28 % for SiHa cells, a significant dose effect (p < 0.01). EP-22 was not less potent at a lower working concentration of 25 g/mL and could reduce HeLa cell viability to 78 %. In this case, there were significant changes in the anti-migratory effect, as evidenced by 45 % inhibition of SiHa cell migration and a 12 % wound closure rate compared with 54 % in the untreated cells. The obtained densitometric analysis indicated that in EP-22 treated HeLa cells, syndecan-1 and perlecan protein levels were reduced by approximately 65 % and 57 %, respectively, while the MMP-2 and MMP-9 levels were reduced to about 50 % and 45 %, respectively. Annexin V staining also highlighted a 40 % enhancement in early apoptosis and 25 % in late apoptosis in EP-22 handled cells. These data suggest the potential of EP-22 and its derivatives as therapeutic molecules in cervical cancer treatment, reducing HeLa proliferation by 35 % and SiHa by 28 %, inhibiting SiHa migration by 45 %, and affecting molecular targets involved in adhesion and invasiveness. Future studies must elucidate the effectiveness of in vivo experiments and how these findings were obtained. At 50 mu g/mL, EP-22 reduced HeLa and SiHa cell viability by 35 % and 28 %, respectively, with significant dose-dependent effects (p < 0.01). At 25 g/mL, EP-22 maintained potency, reducing HeLa cell viability to 78 %. EP-22 inhibited SiHa cell migration by 45 % and reduced wound closure rates to 12 % compared to 54 % in untreated cells. This work uses the HeLa and SiHa cell lines to examine the therapeutic potential of enzyme variation EP-22 in cervical cancer. EP-22 showed significant anti-cancer effects at 50 mu g/mL doses, reducing cell viability at lower concentrations and achieving an IC50 of 35 % for HeLa cells and 28 % for SiHa cells. It is worth mentioning that EP-22 considerably reduced levels of essential proteins: syndecan-1 (65 %), perlecan (57 %), MMP-2 (50 %), and MMP-9 (45 %), in addition to inhibiting SiHa cell migration by 45 %. Furthermore, annexin V staining showed that treated cells exhibited a 40 % increase in early apoptosis and a 25 % increase in late apoptosis.

This paper presents an investigation into the modeling and prediction of the density of supercritical carbon dioxide (SC-CO2) and mole fraction of Erlotinib hydrochloride using machine learning techniques. The dataset consists of temperature and pressure as input variables, with density of SC-CO2 and mole fraction of Erlotinib hydrochloride as output variables. The process is supercritical-based operation which can be used for production of nanomedicines with improved aqueous solubility. Three models, Multilayer Perceptron (MLP), Orthogonal Matching Pursuit (OMP), and Extreme Gradient Boosting (XGB) were trained and optimized using the Firefly Optimization Algorithm (FA). The models’ performance in correlating solubility and density were evaluated via statistical analyses to measure their accuracy. The MLP model achieved high accuracy, with scores of 0.99714 and 0.97749 for density and mole fraction prediction, respectively in term of coefficient of determination (R2). The OMP and XGB models also provided reasonably accurate results. These findings demonstrate the effectiveness of machine learning in understanding and predicting SC-CO2 behavior, with potential applications in industrial processes and pharmaceutical formulations.

OBJECTIVE:To explore whether ovarian-stimulating drugs increase the risk of ovarian cancer in infertile women. METHODS:This meta-analysis involved searching PubMed, Cochrane Library, Web of Science, and Embase. The methodological quality of observational studies was assessed using the modified Newcastle-Ottawa Scale. Data were summarized as OR with 95% CIs. The primary objective was to assess the effect of ovarian-stimulating drugs on ovarian tumors and the secondary objective was to assess this effect in different sub-groups. RESULTS:Forty studies were eligible for this meta-analysis. Overall, compared with unexposed infertile women and unexposed general population, ovarian-stimulating drugs increased the risk of invasive ovarian cancer (OR 1.23, 95% CI 1.14 to 1.32, p =.001) and borderline cancer (OR = 1.32, 95% CI 1.19 to 1.47, p < .001) in women receiving any fertility drugs. Our sub-group analysis showed a higher risk of both invasive and borderline ovarian cancer in infertile women using ovarian-stimulating drugs compared to infertile women with no exposure and the general unexposed population. An increased risk of ovarian cancer was observed in nulliparous women, but not in parous women. In addition, a cumulative clomiphene dose of <900 mg and a number of gonadotropin cycles ≥6 were factors that increased the risk of invasive ovarian cancer. Combined treatment with clomiphene and gonadotropin was associated with an increased risk of borderline cancer. Risk analyses further revealed that prolonged use of oral contraceptives (>60 months) and a family history of ovarian cancer significantly increased the odds of developing ovarian cancer among women treated with ovarian-stimulating drugs. CONCLUSION:Our study showed that ovarian-stimulating drugs increased the risk of ovarian tumors.

Gynecological cancers present significant treatment challenges due to drug resistance and adverse side effects. This review explores advancements in lysosomal escape mechanisms, essential for enhancing nano-therapeutic efficacy. Strategies such as pH-sensitive linkers and membrane fusion are examined, showcasing their potential to improve therapeutic outcomes in ovarian, cervical, and uterine cancers. We delve into novel materials and strategies developed to bypass the lysosomal barrier, including pH-sensitive linkers, fusogenic lipids, and nanoparticles (NPs) engineered for endosomal disruption. Mechanisms such as the proton sponge effect, where NPs induce osmotic swelling and rupture of the lysosomal membrane, and membrane fusion, which facilitates the release of therapeutic agents directly into the cytoplasm, are explored in detail. These innovations not only promise to improve therapeutic outcomes but also minimize side effects, marking a significant step forward in the treatment of ovarian, cervical, and uterine cancers. By providing a comprehensive analysis of current advancements and their implications for clinical applications, this review sheds light on the potential of lysosomal escape strategies to revolutionize gynecological cancer treatment, setting the stage for future research and development in this vital area.

This review explores the evolving landscape of gynecological oncology by focusing on emerging RNA modification signatures as promising biomarkers for assessing the risk and progression of ovarian, cervical, and uterine cancers. It provides a comprehensive overview of common RNA modifications, especially m6A, and their roles in cellular processes, emphasizing their implications in gynecological cancer development. The review meticulously examines specific m6A regulators including “writers”, “readers”, and “erasers” associated with three gynecological cancer types, discussing their involvement in initiation and progression. Methodologies for detecting RNA modifications are surveyed, highlighting advancements in high-throughput techniques with high sensitivity. A critical analysis of studies identifying m6A regulators as potential biomarkers is presented, addressing their diagnostic or prognostic significance. Mechanistic insights into RNA modification-mediated cancer progression are explored, shedding light on molecular pathways and potential therapeutic targets. Despite current challenges, the review discusses ongoing research efforts, future directions, and the transformative possibility of RNA modifications on early assessment and personalized therapy in gynecological oncology.

Endometrial carcinoma (EC) is a prevalent gynecological cancer, and its interaction with the immune system is pivotal in cancer progression. This comprehensive review explores the molecular mechanisms involved in the regulation of EC by tumor-infiltrating immune cells. This review discusses the composition and functions of various immune cell types within the tumor microenvironment, including T cells, B cells, macrophages, and natural killer cells, and elucidates their specific roles in cancer control. It also delves into the immune evasion strategies employed by EC cells, with a specific focus on immune checkpoint pathways and their influence on tumor development. Signaling pathways, cytokines, and chemokines mediating immune responses within the tumor microenvironment are also detailed. Furthermore, clinical implications and therapeutic strategies, such as immunotherapies, are also reviewed, and relevant clinical trials are discussed. Additionally, this review discusses the existing gaps in our knowledge, suggests potential avenues for future research, and emphasizes the significance of understanding these mechanisms for enhanced EC treatment. This review provides an exhaustive overview of the current knowledge, supporting the ongoing quest for more effective therapeutic interventions on EC.

BJOG: An International Journal of Obstetrics & GynaecologyEarly View LETTER TO THE EDITOR The long-term risk of maternal mortality risk after spontaneous preterm birth Xuan Zhang, Xuan Zhang Department of Obstetrics and Gynaecology, Shengjing Hospital of China Medical University, Liaoning, ChinaSearch for more papers by this authorYingying Hao, Corresponding Author Yingying Hao [email protected] Department of Obstetrics and Gynaecology, Shengjing Hospital of China Medical University, Liaoning, China Correspondence Yingying Hao, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No.36, Sanhao Street, Shenyang, Liaoning, 110000, China. Email: [email protected]Search for more papers by this author Xuan Zhang, Xuan Zhang Department of Obstetrics and Gynaecology, Shengjing Hospital of China Medical University, Liaoning, ChinaSearch for more papers by this authorYingying Hao, Corresponding Author Yingying Hao [email protected] Department of Obstetrics and Gynaecology, Shengjing Hospital of China Medical University, Liaoning, China Correspondence Yingying Hao, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No.36, Sanhao Street, Shenyang, Liaoning, 110000, China. Email: [email protected]Search for more papers by this author First published: 22 June 2023 https://doi.org/10.1111/1471-0528.17575Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. REFERENCES 1Theilen LH, Hammad I, Meeks H, Fraser A, Manuck TA, Varner MW, et al. Long-term maternal mortality risk following spontaneous preterm birth: a retrospective cohort study. BJOG. 2023. https://doi.org/10.1111/1471-0528.17552 2Kessous R, Shoham-Vardi I, Pariente G, Holcberg G, Sheiner E. An association between preterm delivery and long-term maternal cardiovascular morbidity. Am J Obstet Gynecol. 2013; 209(4): 368.e1–8. 3Cnattingius S, Villamor E, Johansson S, Edstedt Bonamy AK, Persson M, Wikström AK, et al. Maternal obesity and risk of preterm delivery. JAMA. 2013; 309(22): 2362–70. 4Kolstad KD, Mayo JA, Chung L, Chaichian Y, Kelly VM, Druzin M, et al. Preterm birth phenotypes in women with autoimmune rheumatic diseases: a population-based cohort study. BJOG. 2020; 127(1): 70–8. Early ViewOnline Version of Record before inclusion in an issue ReferencesRelatedInformation

Background Phytosterol is a bioactive compound existing in all plant foods, which might have anticancer properties. The aim of this study was to first assess the impact of the pre-diagnosis phytosterol intake on overall survival (OS) of patients with ovarian cancer (OC). Materials and methods This ambispective cohort study recruited 703 newly diagnosed OC patients to investigate the aforementioned associations. Dietary intake was assessed using a validated 111-item food frequency questionnaire. Deaths were ascertained until March 31, 2021, through active follow-up and medical records. Cox proportional hazards regression models were applied to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results During the median follow-up of 37.17 months, 130 deaths occurred. The median age at diagnosis of 703 OC patients was 53.00 (interquartile: 48.00–60.00) years. Of these, almost half patients (48.08%) were diagnosed in advanced International Federation of Gynecology and Obstetrics (FIGO) stage (III-IV). Additionally, more than half patients were serous carcinoma (68.14%), poorly differentiated (85.21%), and no residual lesions (78.66%). Patients consumed the highest tertile of dietary campesterol (HR = 0.54, 95% CI = 0.31–0.94, P trend < 0.05), stigmasterol (HR = 0.60, 95% CI = 0.37–0.98), and β-sitosterol (HR = 0.63, 95% CI = 0.40–0.99) were significantly associated with better OS compared with those with the lowest tertile of intake. The curvilinear associations were observed between total phytosterols and β-sitosterol intake and OC survival (P non-linear < 0.05). Significant associations were generally consistent across different subgroups stratified by demographical, clinical, and immunohistochemical characteristics. Moreover, there were significant interactions between phytosterol intake and age at diagnosis, body mass index, as well as expressions of Wilms’ tumor-1 and Progestogen Receptor (all P interaction < 0.05). Conclusion Pre-diagnosis higher campesterol, stigmasterol, and β-sitosterol intake were associated with better survival among OC patients.

Introduction: There are limited studies exploring the effects of n-3 PUFA supplementation on pregnancy outcomes. The goal of this study was to review relevant studies in order to determine the effect of n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation on pregnancy outcomes based on eligible randomized controlled trials (RCTs). Material and methods: Qualified studies were searched by keywords in PubMed, the Cochrane library and Embase. Studies from other pertinent sources were also reviewed, and RCTs published before January 2021 were reviewed. For each study, we assessed and synthesized the outcomes by relative risk (RR) or weighted mean difference (WMD) combined with the 95% confidence interval (95% CI). Results: We included 13 studies with 9069 patients. Compared with the control group, n-3 PUFA significantly decreased the incidence of preterm delivery (RR = 0.898, 95% CI: 0.819-0.984) and low birthweight (RR = 0.797, 95% CI: 0.655-0.970), and increased the birth weight (WMD = 99.340, 95% CI: 10.503-188.177) and birth length (WMD = 0.449, 95% CI: 0.236-0.663). There was no significant difference in pregnancy-induced hypertension, preeclampsia, intrauterine growth retardation (IUIG), early preterm delivery, anti-hypertensive therapy, gestational diabetes or head circumference at birth between the two groups. Conclusions: The available evidence shows that n-3 PUFA is not beneficial in reducing the incidence of maternal pregnancy outcomes such as gestational diabetes mellitus and hypertension; but it is beneficial to neonatal health such as decreasing the incidence of preterm delivery and low birthweight and increasing birth weight and birth length.

The aim of the present study was to investigate the effects of human epididymis protein 4 (HE4) on drug resistance and its underlying mechanisms. The associations among proteins were detected by immunoprecipitation and immunofluorescence assays. Then, stably transfected cell lines CAOV3-HE4-L and CAOV3-A2-L expressing HE4 short hairpin (sh)RNAs and ANXA2 shRNAs, respectively, were constructed. MTT assay, immunocytochemistry, western blotting, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and flow cytometry were employed to examine drug sensitivity, as well as the expression and activity of P-glycoprotein (P-gp). HE4 and P-gp in epithelial ovarian cancer tissues were assessed via immunohistochemistry. MicroRNAs that targeted the P-gp gene, ABCB1, were predicted using bioinformatics methods, and their expression was evaluated by RT-qPCR. The common signaling pathways shared by HE4, ANXA2 and P-gp were selected by Gene Set Enrichment Analysis (GSEA). The interaction of HE4, ANXA2 and P-gp were confirmed. P-gp expression was positively associated with HE4 and ANXA2 expression, respectively. Moreover, it was observed that there was no significant rescue of P-gp expression in CAOV3-A2-L cells following the administration of active HE4 protein. In addition, the expression of HE4 and P-gp in ovarian cancer tissues of drug-resistant patients were higher compared with that of the drug-sensitive group (P<0.05). Furthermore, the results revealed that hsa-miR-129-5p was significantly increased accompanied by decreased HE4 or ANXA2 expression and P-gp expression in CAOV3-HE4-L and CAOV3-A2-L cells. GSEA analyses disclosed that HE4, ANXA2 and P-gp genes were commonly enriched in the signaling pathway involved in regulating the actin cytoskeleton. These results indicated that HE4 promotes P-gp-mediated drug resistance in ovarian cancer cells through the interactions with ANXA2, and the underlying mechanism may be associated with decreased expression of hsa-miR-129-5p and dysregulation of the actin cytoskeleton signaling pathway.

Background: The goal of this study was to review relevant studies in order to determine the effect of n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation on pregnancy outcomes based on eligible randomized controlled trails (RCTs). Method: Qualified studies were searched by keywords in PubMed, Cochrane and Embase. Studies from other pertinent sources were also reviewed, RCT studies published before January 2021 were reviewed. For each study, we assessed and synthesized the outcomes by relative risk (RR) or weighted mean difference (WMD) combined with 95% confidence interval (95% CI). Result: We included 29 studies with 5623 patients. Compared with the control group, n-3 PUFA significantly decreased the incidence of preterm delivery (PD) (RR: 0.898, 95%CI: 0.819~0.984), low birthweight (RR: 0.797, 95%CI: 0.655~0.970), and preeclampsia (RR: 0.814, 95%CI: 0.687~0.966); increased the birth weight (WMD: 99.340, 95%CI: 10.503~188.177) and birth length (WMD: 0.449, 95%CI: 0.236~0.663). There was no significant difference in PIH, IUIG, early PD, anti-hypertensive therapy, gestational diabetes and head circumference at birth between the two groups. Conclusion : The available evidence shows that n-3 PUFA is not beneficial in reducing the incidence of maternal pregnancy outcomes such as gestational diabetes mellitus and hypertension, but it is beneficial to neonatal health.

Background: The associations of the consumption of cruciferous vegetables (CVs) and their bioactive components, isothiocyanates (ITCs), with ovarian cancer (OC) mortality have been unclear, owing to limited studies and inconsistent findings. To date, no studies have evaluated these associations among Chinese patients with OC. This study aims to provide more evidence indicating the relationships of pre-diagnosis CVs and ITC intake with OC survival. Methods: We examined the associations of pre-diagnosis CV and ITC intake with OC mortality in a hospital-based cohort (n = 853) of Chinese patients with epithelial OC between 2015 and 2020. Pre-diagnosis dietary information was evaluated with a validated food frequency questionnaire. Deaths were ascertained until March 31, 2021 via medical records and active follow-up. The associations were examined with the Cox proportional hazards model, adjusted for potential confounders, and stratified by menopausal status, residual lesions, histological type, and body mass index (BMI). Results: During a median follow-up of 37.2 months (interquartile: 24.7–50.2 months), we observed 130 deaths. The highest tertile of total CV intake was associated with better survival than the lowest tertile intake [hazard ratio (HR) = 0.57, 95% confidence interval (CI) = 0.33–0.98, p trend < 0.05]. In addition, higher intake of ITCs from CVs was associated with better survival (HRT3VS.T1 = 0.59, 95% CI = 0.36–0.99, p trend = 0.06). Significant inverse associations were also observed for subgroup analyses stratified by menopausal status, residual lesions, histological type, and BMI, although not all associations showed statistical significance. Conclusion: Increasing pre-diagnosis consumption of CVs and ITCs was strongly associated with better survival in patients with OC.

Aims: Tomoregulin-2 (TMEFF2) is a single-pass transmembrane protein whose specific functions and mechanisms in endometrial carcinoma (EC) remain unclear. The aim of this study was to investigate the expression, prognostic role, and potential regulatory mechanisms of TMEFF2 in EC. Materials and methods: The expression and prognosis of TMEFF2 in EC were analyzed via bioinformatics and verified by immunohistochemistry and survival analysis. Proliferation, invasion, and migration of EC cells in vitro were assessed by cell functional assays, while epithelial-mesenchymal transition (EMT) markers and key signaling pathway proteins were evaluated by western blotting. Key findings: The expression of TMEFF2 in EC was significantly higher than that in atypical hyperplasia and normal endometrium, the high expression of TMEFF2 was correlated with advanced stage, poor differentiation, and lymph node metastasis, and also predicted a poor prognosis of EC. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that TMEFF2 and its related genes were enriched in the central nervous system, cell adhesion, signal transduction, and several critical signaling pathways. We also elucidated TMEFF2 networks of kinase, microRNA, and transcription factor targets. In vitro, the proliferation, invasion, and migration abilities of EC cells decreased after TMEFF2 downregulation. Downregulation of TMEFF2 reduced the activation of MAPK and PI3K signaling pathways, and inhibited EMT. Significance: TMEFF2 plays an important role in the initiation, development, and malignant behavior of EC and can be a potential target for early diagnosis and treatment in EC.

目的:探讨Rab23在卵巢上皮性浆液性囊腺癌组织中的表达情况及其与卵巢癌患者临床病理参数及预后的相关性.方法:利用免疫组化SP法检测Rab23在59例卵巢上皮性浆液性囊腺癌、10例卵巢上皮性交界性肿瘤组织、13例卵巢上皮性良性肿瘤组织以及20例正常卵巢组织中表达情况,进一步分析其与卵巢癌患者临床病理参数及预后的关系.结果:Rab23主要以细胞质、细胞膜着色.Rab23在卵巢上皮性浆液性囊腺癌中阳性表达率(84.7％,50/59)明显高于良性组(30.8％,4/13)及正常卵巢组织(25％,5/20)(P均<0.05).在卵巢上皮性浆液性囊腺癌中,Rab23阳性表达与FIGO分期晚期(P<0.01)和分化程度(P<0.05)具有相关性,是影响卵巢癌患者总生存时间和预后的独立危险因素.结论:Rab23与卵巢癌的发生、发展及预后有关,有望成为卵巢癌患者评估预后、靶向治疗的分子标志物.

Transforming growth factor-β, a cell secretion factor of the TGF-β superfamily, is involved in the regulation of cell proliferation, differentiation, cytoskeleton formation, migration, invasion and other biological behaviors. Autophagy and mitophagy play an important role in tumor progression by regulating self-digestion, and degradation and reuse of cells and mitochondria. In this study, changes in autophagy and mitophagy processes in ovarian cancer cells under TGF-β1 treatment were detected via Western blot and immunofluorescence, as well as the role of fucosylation modification. Changes in mitochondrial membrane potential in response to TGF-β1 and fucosylation were detected via immunofluorescence. The effects of TGF-β1 and its fucosylation on autophagic flux were further determined by transient transfection of cells with Ad-mRFP-GFP-LC3 adenovirus. TGF-β1 clearly promoted autophagy and mitophagy in ovarian cancer cells. TGF-β1 fucosylation stimulated these regulatory effects on ovarian cancer cells via modulation of PI3K/Akt and Ras-Raf-MEK-ERK pathways through TAK1. Our collective data support the physiological significance of TGF-β1 and provide a novel direction for targeted therapy for ovarian cancer.