Constructing a Prognostic Model of Uterine Corpus Endometrial Carcinoma and Predicting Drug-Sensitivity Responses Using Programmed Cell Death-Related Pathways.

Background: Uterine Corpus Endometrial Carcinoma (UCEC) is the most common type of cancer that develops in the uterus, specifically originating from the endometrium, the inner lining of the uterus. Programmed cell death (PCD) is a highly regulated process that eliminates damaged, aged, or unwanted cells in the body. Dysregulation of PCD pathways can contribute to the formation and progression of various cancers, including UCEC. Methods: Fourteen PCD pathways (autophagy-dependent cell death, alkaliptosis, apoptosis, cuproptosis, entotic cell death, ferroptosis, immunogenic cell death, lysosome-dependent cell death, MPT-driven necrosis, necroptosis, netotic cell death, oxeiptosis, parthanatos, and pyroptosis) were involved in building a prognostic signature. The model was trained and tested using data from the TCGA-UCEC and validated with the GSE119041 dataset. Results: A 12-gene PCD signature (DRAM1, ELAPOR1, MAPT, TRIM58, UCHL1, CDKN2A, CYFIP2, AKT2, LINC00618, TTPA, TRIM46, and NOS2) was established and validated in an independent dataset. UCEC patients with a high PCD score (PCDS) exhibited worse prognosis. Furthermore, PCDS was found to be associated with immune related cells and key tumor microenvironment components through multiple methods. It was observed that UCEC patients with a high PCD score may not benefit from immunotherapy, but some chemo drugs like Bortezomib may be useful. Conclusion: In conclusion, a novel PCD model was established by comprehensively analyzing diverse cell death patterns. This model accurately predicts the clinical prognosis and drug sensitivity of UCEC. The findings suggest that the PCD signature can serve as a valuable tool in assessing prognosis and guiding treatment decisions for UCEC patients.

Shikonin reduces M2 macrophage population in ovarian cancer by repressing exosome production and the exosomal galectin 3-mediated ß-catenin activation.

BACKGROUND: Shikonin (SK), a naphthoquinone with anti-tumor effects, has been found to decrease production of tumor-associated exosomes (exo). This study aims to verify the treatment effect of SK on ovarian cancer (OC) cells, especially on the production of exo and their subsequent effect on macrophage polarization. METHODS: OC cells SKOV3 and A2780 were treated with SK. The exo were isolated from OC cells with or without SK treatment, termed OC exo and SK OC exo, respectively. These exo were used to treat PMA-induced THP-1 cells (M0 macrophages). M2 polarization of macrophages was determined by measuring the M2 specific cell surface markers CD163 and CD206 as well as the secretion of M2 cytokine IL-10. The functions of galectin 3 (LGALS3/GAL3) and ß-catenin in macrophage polarization were determined by gain- or loss-of-function assays. CB-17 SCID mice were subcutaneously injected with SKOV3 cells to generate xenograft tumors, followed by OC exo or SK OC exo treatment for in vivo experiments. RESULTS: SK suppressed viability, migration and invasion, and apoptosis resistance of OC cells in vitro. Compared to OC exo, SK OC exo reduced the M2 polarization of macrophages. Regarding the mechanism, SK reduced exo production in cancer cells, and it decreased the protein level of GAL3 in exo and recipient macrophages, leading to decreased ß-catenin activation. M2 polarization of macrophages was restored by LGALS3 overexpression but decreased again by the ß-catenin inhibitor FH535. Compared to OC exo, the SK OC exo treatment reduced the xenograft tumor growth in mice, and it decreased the M2 macrophage infiltration within tumor tissues. CONCLUSION: This study suggests that SK reduces M2 macrophage population in OC by repressing exo production and blocking exosomal GAL3-mediated ß-catenin activation.

Clear cell carcinoma arising in an ovarian remnant 19 years after oophoerctomy: case report.

BACKGROUND: Ovarian remnant syndrome (ORS) is a rare complication that occurs after oophorectomy, characterized by residual ovarian tissue causing pelvic pain, masses, and various symptoms. The clinical manifestations of ORS are nonspecific, and its diagnosis relies on histological examination. Since ORS typically represents a benign ovarian lesion, there have been few reported cases of malignant transformation. In this report, we presented a unique case of ovarian clear cell carcinoma (OCCC) arising from an ovarian remnant following salpingo-oophorectomy. CASE PRESENTATION: Our patient was a 47-year-old female initially diagnosed with uterine myoma. She had previously undergone cesarean section and unilateral salpingo-oophorectomy. Transvaginal ultrasound and computed tomography (CT) scans revealed a soft tissue mass adjacent to the right lateral wall of the myometrium. The patient opted for transabdominal hysterectomy, left adnexal resection, laparoscopic omentectomy, appendectomy, and pelvic and abdominal lymphadenectomy. The final pathology results confirmed the diagnosis of OCCC, consistent with ORS. The patient subsequently received six cycles of intravenous chemotherapy using the carboplatin/paclitaxel (TC) regimen (paclitaxel liposomes 175 mg/m², carboplatin AUC 5). After 3 years of follow-up, the patient's condition remained normal. CONCLUSION: ORS can significantly impact patients' quality of life and pose challenges for clinicians. Complete excision of ovarian tissue during the initial surgery is crucial in preventing ORS recurrence and potential malignant transformation of ovarian remnants.

The role of inflammatory factors and T-cell subsets in the diagnosis of recurrence in epithelial ovarian cancer patients and the effect of olaparin treatment on them.

BACKGROUND: The aim of the study is to investigate the role of serum inflammatory factors and T-cell subsets in the diagnosis of recurrence in epithelial ovarian cancer patients and the effect of olaparib on inflammatory factor and T-lymphocyte subsets in patients with recurrent epithelial ovarian cancer. METHODS: In this study, 100 patients diagnosed as recurrent epithelial ovarian cancer in our hospital and 100 patients without recurrent epithelial ovarian cancer in the same period were selected. According to the treatment plan, the recurrent patients were divided into conventional therapy group (Paclitaxel and Carboplatin) and combined therapy group (Paclitaxel, Carboplatin, and olaparib). The levels of serum inflammatory factors were evaluated by enzyme-linked immunosorbent assay. The peripheral blood T-lymphocyte subsets in each group were detected by flow cytometry. RESULTS: Compared with nonrecurrent patients, recurrent patients have higher serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels (p < .05), and lower interferon-γ (IFN-γ) level and the CD4+/CD8+ ratio. After adjusting for confounding factors, the results showed that the serum IL-6, IFN-γ, and TNF-α levels were influencing factors of recurrence in epithelial ovarian cancer patients. The area under the receiver operating curve and the sensitivity of serum TNF-α in predicting ovarian cancer recurrence were higher than those of IL-6 and IFN-γ. After secondary chemotherapy and/or olaparib maintenance treatment, the IL-6 (p < .001) and TNF-α (p < .001) levels in combined therapy group were lower than those in the conventional therapy, whereas the IFN-γ level (p < .001), the CD4+ T-cell proportion (p = .0069) and the CD4+/CD8+ ratio (p = .0201) were higher than those in the conventional therapy. CONCLUSION: The serum IL-6, TNF-α, and IFN-γ levels were closely related to the recurrence of ovarian cancer. Olaparib maintenance treatment can significantly decrease the IL-6 and TNF-α level, and increase IFN-γ level and the CD4+/CD8+ ratio in patients with recurrent ovarian cancer.

CT radiomics prediction of CXCL9 expression and survival in ovarian cancer.

BACKGROUND: C-X-C motif chemokine ligand 9 (CXCL9), which is involved in the pathological processes of various human cancers, has become a hot topic in recent years. We developed a radiomic model to identify CXCL9 status in ovarian cancer (OC) and evaluated its prognostic significance. METHODS: We analyzed enhanced CT scans, transcriptome sequencing data, and corresponding clinical characteristics of CXCL9 in OC using the TCIA and TCGA databases. We used the repeat least absolute shrinkage (LASSO) and recursive feature elimination(RFE) methods to determine radiomic features after extraction and normalization. We constructed a radiomic model for CXCL9 prediction based on logistic regression and internal tenfold cross-validation. Finally, a 60-month overall survival (OS) nomogram was established to analyze survival data based on Cox regression. RESULTS: CXCL9 mRNA levels and several other genes involving in T-cell infiltration were significantly relevant to OS in OC patients. The radiomic score (rad_score) of our radiomic model was calculated based on the five features for CXCL9 prediction. The areas under receiver operating characteristic (ROC) curves (AUC-ROC) for the training cohort was 0.781, while that for the validation cohort was 0.743. Patients with a high rad_score had better overall survival (P < 0.001). In addition, calibration curves and decision curve analysis (DCA) showed good consistency between the prediction and actual observations, demonstrating the clinical utility of our model. CONCLUSION: In patients with OC, the radiomics signature(RS) of CT scans can distinguish the level of CXCL9 expression and predict prognosis, potentially fulfilling the ultimate purpose of precision medicine.

Caseinate-reinforced pectin hydrogels: Efficient encapsulation, desirable release, and chemical stabilization of (-)-epigallocatechin.

(-)-Epigallocatechin (EGC) has good health benefits, but its chemical stability is low. Pectin hydrogels have potential for the encapsulation and delivery of EGC, but they are limited by porous networks and poor mechanical properties. In this study, protein (whey protein isolate and caseinate)-reinforced pectin hydrogel beads (HBPEC-WPI and HBPEC-CAS) were developed to overcome these limitations. The results showed that HBPEC-CAS was a superior delivery system for EGC. HBPEC-CAS had a compact network structure, mainly because of the hydrogen bonds that formed between caseinate and pectin. Moreover, the EGC encapsulation efficiency of HBPEC-CAS (2.4%) reached 92.23 %; HBPEC-CAS (2.4%) could also delay the release of EGC in an aqueous environment, while ensuring its sufficient release in a simulated gastrointestinal environment. Notably, EGC was chemically stabilized in HBPEC-CAS (2.4%) during a 6-day storage period at 37 °C through the inhibition of its epimerization, oxidation, dimerization, and trimerization. The numerous hydroxyl groups in EGC readily interacted with the exposed amino acid residues in caseinate and created more protective sites. This study developed a strategy for protein-reinforced pectin hydrogel development and approaches for the protection of tea polyphenols; the findings offer useful insights for the tea-based food and beverage industry.

IGF2BP2 promotes the progression of ovarian endometriosis by regulating m6A-modified MEIS2 and GATA6.

BACKGROUND: m6A-RNA modification mediated by the N6-methyladenosine RNA methylation-related molecule methyltransferase-like 3 has been implicated in the progression of endometriosis. However, the functions of other m6A regulators, especially in ovarian endometriosis, remain unknown. METHODS: Three datasets (GSE7305, GSE7307, and GSE37837) with diagnosed ovarian endometriosis were extracted from the Gene Expression Omnibus database. Using bioinformatics methods such as Weighted Gene Co-expression Network Analysis, Gene Ontology analysis, protein-protein interaction, and correlation, hub genes were identified. Using dot blot and N6-methyladenosine-IP-qPCR, the total and individual N6-methyladenosine gene levels were quantified. On clinical ovarian ectopic and eutopic endometrium tissues, N6-methyladenosine RNA methylation sequencing was performed. To authenticate protein localization and expression level, immunohistochemical staining and western blot were conducted, respectively. The database Connectivity Map was used to predict small molecules with potential therapeutic effects. RESULTS: In ovarian endometriosis, the N6-methyladenosine "reader" molecule IGF2BP2 and related target genes MEIS2 and GATA6 were highly expressed. IGF2BP2 promoted the proliferation, migration, and invasion of ectopic endometrial stromal cells by stabilizing the mRNA of MEIS2 and GATA6. Synergistically, METTL3 and IGF2BP2 increased the N6-methyladenosine methylation of MEIS2 and GATA6. We developed five molecules (Mercaptopurine, MK-886, CP-863187, Canadine, and Securinine) that could be used to treat ovarian endometriosis based on IGF2BP2. CONCLUSION: Our findings provided additional support for a systematized understanding of the role of N6-methyladenosine RNA methylation in endometriosis and confirmed for the first time the mechanism of IGF2BP2 in promoting ovarian endometriosis. This provides the molecular foundation for potential future therapies for ovarian endometriosis. DATA AVAILABILITY: The data used to support the findings of this study are available from the corresponding author upon request.

Use of targeted therapy and immunotherapy for the treatment of yolk sac tumors in extragonadal pelvic sites: two case reports.

We present the clinicopathologic features and treatments of two cases of extragonadal yolk sac tumor (EGYST) detected in young females, including one in the myometrium admitted in 2013 and another in the serosal layer of the anterior wall of uterus admitted in 2019. The following details were recorded: patient age, clinical presentation, tumor location, International Federation of Gynecology and Obstetrics (FIGO) stage (where applicable), histologic patterns including Schiller-Duval (SD) bodies, other germ cell or somatic components, immunoperoxidase results, treatment, and outcome. The patients were aged 18 and 32 years old, both displayed the clinical manifestation of pain in the lower abdomen, tumor sizes were 10 and 8 cm, respectively, and alpha-fetoprotein (AFP) was significantly increased (1,210-20,251.0 ng/mL). Both participants underwent surgery and typical SD bodies were observed in postoperative pathology. Immunohistochemistry (IHC) results indicated that they were AFP positive (+) and Sal-like protein 4 (SALL4) (+). Both patients received multi-line chemotherapy after surgery, and participant 2 received targeted therapy and immunotherapy. At 36 months after surgery, one patient died, and the other was still receiving treatment. The benefit of germ cell appropriate chemotherapy in somatically derived EGYST has not been fully elucidated. Our report first showed that it is possible to reduce the recurrence rate and improve the prognosis of patients with EGYST by adding targeted therapy and immunotherapy (bevacizumab + tislelizumab) to traditional chemotherapy regimens.

STK17B promotes the progression of ovarian cancer.

BACKGROUND: Protein kinase is increasingly receiving widespread attention because of its role in the tumor progression. Serine/threonine protein kinase (STK) is an important family involved in the development of a variety of cancers. Many studies have shown that serine/threonine kinase 17B (STK17B) is highly expressed in a variety of malignant tumors and participate in proliferation and metastasis. However, the exact function of STK17B remains uncertain in ovarian cancer. Our study aims to investigate whether STK17B plays a role in the occurrence and development of epithelial ovarian cancer. METHODS: We employed quantitative reverse transcription polymerase chain reaction to detect the relative expression of STK17B in ovarian cancer tissues. STK17B was down-regulated and up-regulated in ovarian cancer cell lines by small interfering RNA and overexpressed plasmid, respectively. The effects of STK17B on proliferation, invasion and migration of ovarian cancer cells in vitro were analyzed by CCK-8 test, Transwell test, scratch test and EDU test. The tumorigenicity of subcutaneous xenograft tumor in nude mice to study the role of STK17B in tumorigenesis in vivo. Western Blotting analysis revealed that STK17B and EMT. RESULTS: STK17B expression was significantly increased in ovarian cancer tissues. The STK17B silencing suppressed cell progression, while the overexpression of STK17B promoted progression in vivo or in vitro. Western bolt showed that STK17B increased the invasion and migration of ovarian cancer cell by promoting the EMT process. CONCLUSIONS: STK17B was highly expressed in epithelial ovarian cancer tissues and increased the proliferation, invasion and migration of ovarian cancer cells by promoting EMT process.

Osthole Inhibits Breast Cancer Progression through Upregulating Tumor Suppressor GNG7.

Osthole (OST) is a plant-derived compound that can inhibit the proliferation of tumor cells and has a tumor-suppressive effect in multiple types of cancers. However, the mechanisms of OST-mediated breast cancer (BrCa) inhibition were still largely unknown. In this study, we made full use of the GSE85871 dataset to identify potential targets of OST in BrCa via multiple bioinformatics analysis. Next, a series of in vitro experiments were conducted to check the role of GNG7 in BrCa and the relationship between OST and GNG7. Through a series of bioinformatics analyses, GNG7 was identified as a potential target of OST, which could be significant upregulated by OST exposure in BrCa cells. Besides, GNG7 was lowly expressed in BrCa tissues compared with normal breast tissues, and BrCa patients with low GNG7 expression had shorter overall survival (OS) and relapse-free survival (RFS) compared with those with high GNG7 expression. Moreover, GNG7 silencing significantly enhanced cell proliferation and inhibited apoptosis, and exogenous overexpression of GNG7 showed reverse effects on BrCa cells. Last but not least, GNG7 inhibition could notably rescue OST-mediated cytotoxic effects. In summary, we identified GNG7 as a novel target for OST in BrCa and a potential tumor suppressor. Thus, OST could be therapeutically beneficial for BrCa through a GNG7-dependent mechanism.

Construction of a nine DNA repair-related gene prognostic classifier to predict prognosis in patients with endometrial carcinoma.

BACKGROUND: Endometrial cancer (EC) is one of the most common gynecological malignancies worldwide. However, the molecular mechanisms and the prognostic prediction for EC patients remain unclear. METHODS: In the current study, we performed an in-depth analysis of over 500 patients which were obtained from the Cancer Genome Atlas (TCGA) database. The bioinformatics analysis included gene set enrichment analysis (GSEA) and Cox and lasso regression analyses to ensure overall survival (OS)-related genes, moreover, to construct a prognostic model and a nomogram for EC patients. RESULTS: GSEA identified 4 gene sets significantly associated with EC, which are DNA repair, unfolded protein response, reactive oxygen species pathway and UV response up. Twenty-five OS-related DNA repair genes were screened out, after that, a 9-mRNA signature was constructed to measure the risk scores of patients with different outcomes. In addition, a nomogram contained the 9-mRNA model and clinical parameters was also presented to assess the prognosis. Patients with low risk were more likely to have sensitivity to paclitaxel, vinblastine, rapamycin, metformin, imatinib, Akt inhibitor and lapatinib. CONCLUSIONS: The identified highly enriched gene sets may offer a novel insight into the tumorigenesis and treatment of EC. Additionally, the constructed 9-mRNA model and the nomogram have prominent clinical implications for prognosis evaluation and specific therapy guidance for EC patients.

Analysis of factors related to fertility after endometriosis combined with infertility laparoscopic surgery.

To investigate the influence factors of laparoscopic postoperative pregnancy of patients with endometriosis and infertility, further validate the application of EFI scoring system in endometriosis, and to improve the pregnancy rate.A total of 258 patients with endometriosis and infertility who underwent laparoscopic surgery and follow-up treatment at Wuxi Maternal and Child Health Hospital from January 2015 to December 2016 were selected and divided into pregnant and non-pregnant groups according to whether they were pregnant. All patients were divided into 4 groups according to EFI score: group with EFI score ≥9, 7-8, 4-6, and <4, and divided into I, II, III, and IV groups according to AFS stages. The uterus-laparoscopic surgery was performed. The patients were followed up for 3 years. The factors affecting the pregnancy rate were analyzed. The pregnancy rate and pregnancy types were calculated at different time points.Multivariate analysis showed that age <35 years, infertility time <5 years, secondary infertility, EFI score, postoperative ART application were protection factors of postoperative pregnancy. The 3-year cumulative postoperative pregnancy rate was 75.6%. The cumulative pregnancy rate was 92.2% in group with EFI score ≥9, 85.9% in group with EFI score 7-8, 62.5% in group with EFI score 4-6 and 5.9% in group with EFI score <4, there was significant difference between the 4 groups (P < .05). The proportion of pregnancies in 6 months and 12 months was higher in patients with EFI score ≥7, 61.0% in patients with EFI score ≥9 and 41.1% in patients with EFI score ≥7. The highest natural pregnancy rate was 83.1% in group with EFI score ≥9, and there was significant difference between the 4 groups (P < .05).Age <35 years, infertility time <5 years, secondary infertility, EFI score and ART application were the protective factors of postoperative pregnancy. EFI score had positive significance in predicting and guiding the postoperative pregnancy of patients with endometriosis and infertility. According to EFI score, the pregnancy rate of patients with endometriosis and infertility can be significantly improved by strict management and active pregnancy program.

Citrus Oil Emulsions Stabilized by Citrus Pectin: The Influence Mechanism of Citrus Variety and Acid Treatment.

Citrus pectin and citrus oil are the main functional components of citrus residuals in the processing industry. In this study, citrus oil emulsions were fabricated for the first time using four different citrus pectins (orange, mandarin, grapefruit, and commercial citrus pectins) as the emulsifier. The influence mechanism of citrus variety and acid treatment (pH 1, 2, 3, 4, 5, 6, and 7) on the emulsifying capacity of citrus pectins was systematically investigated by understanding the relationship between molecular structure, solution property, interfacial property, and emulsion property. The results suggest that citrus variety and acid treatment can significantly influence the emulsifying capacity in relation to the molecular structure and molecular state of citrus pectins. A smaller molecular size of citrus pectin and lower pH between 2 and 7 produced a reduction in aggregate size, which improved the interfacial capacity and emulsifying ability by promoting their distribution at the interface. Although hydrolyzed citrus pectins at pH 1 with a lower molecular size exhibited better interfacial capacity, citrus oil emulsions were unstable due to electrostatic attraction caused by partially positive charged citrus pectins. Fine stable citrus oil emulsion was prepared using mandarin pectin with a relative high methyl ester content and small molecular size at pH 2. Our results provide a scientific basis for the fabrication of citrus oil emulsion based on citrus pectin and facilitate the application of citrus residuals in the food industry.

The stability of three different citrus oil-in-water emulsions fabricated by spontaneous emulsification.

In this study, emulsions were prepared through spontaneous emulsification, using three different citrus oils as the oil phase and Tween 80 as the surfactant. Utilizing 4% Tween 80, three types of citrus oil emulsions were prepared with small particle size, monomodal distribution and high transmission. After 24 h, each emulsion exhibited different degrees of gravitational separation. Mandarin oil emulsions were the most unstable, showing coalescence of small droplets with an obvious cream layer formed at 9 h. Bergamot oil emulsions possessed small droplets with the best stability over 24 h, due to their relatively polar components (e.g. linalyl acetate) and water-insoluble constituents (e.g. γ-terpinene). These results suggest that the emulsifying properties and instability mechanism of citrus oil emulsions are strongly dependent on the inherent properties and composition of citrus oils. This study is significant for the development of an effective strategy to improve the stability of citrus oil-based colloidal systems.

Decreased miR-320 expression is associated with breast cancer progression, cell migration, and invasiveness via targeting Aquaporin 1.

Our previous studies have demonstrated that Aquaporin 1 (AQP1) is overexpressed in breast cancer. However, the mechanism remains elusive. MicroRNA 320 (miR-320) downregulation has been reported in various types of cancers, and it may regulate AQP1 expression. In this study, miR-320 and AQP1 expressions were investigated by quantitative reverse transcription-PCR, in situ hybridization, and immunohistochemistry. The clinicopathological implications of these molecules were also analyzed. We found that miR-320 expression is downregulated in both plasma and tumor tissue in human breast cancer patients. Survival analysis showed that reduced expression of miR-320 and overexpression of AQP1 are associated with worse prognosis. Luciferase assays showed that miR-320 negatively regulates AQP1 expression. In addition, cell proliferation, migration, and invasion assays were performed to investigate the effects of miR-320 on breast cancer cells. Our results showed that miR-320 overexpression inhibits cell proliferation, migration, and invasion in breast cancer cells by downregulating AQP1. These observations suggested that miR-320 downregulation may enhance AQP1 expression in breast cancer, favoring tumor progression. Our findings indicated that miR-320 and AQP1 may serve as prognostic biomarkers and therapeutic targets in the treatment of breast cancer.

Effects of Preheating and Storage Temperatures on Aroma Profile and Physical Properties of Citrus-Oil Emulsions.

Citrus oils are used as good carrier oil for emulsion fabrication due to their special flavor and various health-promoting functions. In this study, the effects of preheating temperature (30, 40, 50, 60, and 70 °C) and storage temperature (4, 25, and 37 °C) on aroma profiles and physical properties of three citrus-oil (i.e., mandarin, sweet orange, and bergamot oils) emulsions were systematically investigated for the first time. The results demonstrated the significant impact of temperature on aroma profile and physical properties. The abundance of d-limonene was found to be the main factor determining the aroma of the three citrus-oil emulsions at different preheating and storage temperatures, while ß-linalool and linalyl acetate were important for the aroma of bergamot oil emulsion. Preheating temperature showed a profound impact on the aroma of citrus-oil emulsions, and the aroma of different citrus oil emulsions showed different sensitivity to preheating temperature. Storage temperature was also able to alter the properties of citrus oil emulsions. The higher was the storage temperature, the more alteration of aroma and more instability of the emulsions there was, which could be attributed to the alteration of the oil components and the properties of emulsions. Among all three emulsions, bergamot-oil emulsion was the most stable and exhibited the most potent ability to preserve the aroma against high temperature. Our results would facilitate the application of citrus-oil emulsions in functional foods and beverages.