A clinical prognostic model of oxidative stress-related genes linked to tumor immune cell infiltration and the prognosis of ovarian cancer patients.

Background: According to statistics, ovarian cancer (OV) is the most prevalent type of gynecologic malignancy and has the highest mortality rate of all gynecologic tumors. Although several studies have shown that oxidative stress (OS) contributes significantly to the onset and progression of cancer, the role of OS in OV needs to be investigated further. Thus, it is critical to comprehend the function of OS-related genes in OV. Methods: In this study, all data related to the transcriptome and clinical status of the patients were retrieved from "The Cancer Genome Atlas" (TCGA) and "Gene Expression Omnibus" (GEO) databases. Using the unsupervised cluster analysis technique, all patients with OV were classified into two different subtypes (categories) based on the OS gene. All hub genes were screened using the weighted gene co-expression network analysis (WGCNA). Since the hub genes and the differentially expressed genes (DEGs) in both categories were found to intersect, the univariate Cox regression analysis was implemented. A multivariate Cox analysis was also performed to construct a novel clinical prognosis model, which was validated using data from the GEO cohort. In addition, the relationship between risk score and immune cell infiltration level was evaluated using CIBERSORT. Finally, qRT-PCR was used to confirm the expression of the genes used to construct the model. Results: Two subtypes of OS were obtained. The findings indicated that OS-C1 had a better survival outcome than OS-C2. The results of WGCNA yielded 112 hub genes. For univariate COX regression analyses, 49 OS-related trait genes were obtained. Finally, a clinical prognostic model containing two genes was constructed. This model could differentiate between patients with OV having varying years of survival in the TCGA and GEO cohorts. The model risk score was verified as an independent prognostic indicator. According to the results of CIBERSORT, many tumor-infiltrating immune cells were found to be significantly related to the risk score. Furthermore, the results revealed that patients with low-risk OV in the CTLA4 treatment group had a high likelihood of benefiting from immunotherapy. qRT-PCR results also showed that the expression of MARVELD1 and VSIG4 was high in the OV samples. Conclusions: Analysis of the results suggested that the newly developed model, which contained two characteristic OS-related genes, could successfully predict the survival outcomes of all patients with OV. The findings of this study could offer valuable information and insights into the refinement of personalized therapy and immunotherapy for OV in the future.

Function of homocysteine and HE4 in endometrial carcinoma: verified by prospective experiment.

Background: Timely diagnosis is the key factor to improve the prognosis of endometrial carcinoma (EC). To date, no particularly good markers could significantly improve the detection rate of EC. This study aimed to assess the utility of serum markers homocysteine (Hcy), human epididymal protein 4 (HE4), cancer antigen 199 (CA199), cancer antigen 125 (CA125), fibrinogen (Fib), and D-dimer (D-D) for EC diagnosis, especially Hcy of which its role in EC has not been noticed. Methods: Pre-test and verification tests were performed. In Pre-test, the diagnostic value of the included markers was evaluated and the right marker was chosen to establish an efficient new risk index for screening EC. In verification tests, the applicability of the new risk index was tested. Several evaluation indices including receiver operating characteristic (ROC) curve, Youden Index, sensitivity (SN), and specificity (SP), were adopted to assess the diagnostic value of the included markers for EC. Results: Hcy may be useful in the diagnosis of EC. Its diagnostic value was not significantly lower than that of HE4. Based on the diagnostic value of Hcy and HE4, a new risk index was established, which demonstrated high value in EC diagnosis (ROC, 0.801), especially among young female patients (age ≤50 years, ROC, 0.871). Furthermore, the level of Hcy, but not HE4, was notably different in normal or benign endometrial lesions, atypical endometrial hyperplasia (AEH), and EC. Conclusions: The change of Hcy levels could be used to diagnose EC and when taken into consideration together with the detection of HE4, the diagnostic accuracy of EC is further improved.

Dynamic changes at high-protein dietary pattern of major fatty acids in healthy lactating women: A systematic review and meta-analysis.

BACKGROUND: Fatty acids (FAs) in human milk are important nutrients for infants. They play important roles in energy supply, nervous system development, and metabolic function maintenance. However, how the composition of major milk FAs change with lactation stages remains controversial. OBJECTIVES: To systematically review the concentration range of major FAs in human milk at various lactation stages. METHODS: A total of 12 papers involving 50 sets of data with 3507 participants were reviewed according to the PRISMA checklist and flow diagram. The inclusion criteria was the literatures had the FAs contents in breast milk of healthy lactation mothers at three lactation stages and the dietary patterns could be calculated. The exclusion criteria were: the studies were duplicates, were unrelated to dietary patterns or breast milk composition, and/or the study populations were unhealthy. We searched PubMed, the China National Knowledge Infrastructure, WanFang, and Web of science. Agency for Health Care Research and Quality (AHRQ) was used to assess the bias of studies. The mean values of polyunsaturated fatty acids (PUFAs) including docosahexaenoic acid (DHA), arachidonic acid (AA), eicosapentaenoic acid (EPA), α-linolenic acid (ALA), linoleic acid (LA), monounsaturated fatty acids (MUFAs), and saturated fatty acids (SFAs, including lauric acid and palmitic acid), in human milk at three lactation stages (colostrum 1-7 d, transitional milk 8-14 d, mature milk 15 d-3 mo) of healthy lactating women were investigated in terms of the high protein dietary pattern. Publication biases were evaluated by Egger's test. RESULTS: According to the percentage in total fat of colostrum, transitional milk, and mature milk (% wt/wt), respectively, the results showed that PUFA (25.72%, 24.92%, and 22.69%), AA (0.85%, 0.76%, and 0.59%), DHA (0.53%, 0.47%, and 0.39%), EPA (0.15%, 0.10%, and 0.10%), and MUFA (37.39%, 37.21%, and 36.14%) contents in breast milk decreased with lactation, while another two PUFA forms, LA (17.47%, 17.82%, and 17.48%), and ALA (1.09%, 1.39%, and 1.24%) arrived at a peak in the transitional milk and then decreased in the mature milk, SFA (37.46%, 38.64%, and 40.52%), and lauric acid contents (2.78%, 4.91%, and 4.97%) increased with the lactation stages. CONCLUSION: These findings could shed light on the dynamic change progress of major FA metabolism, potentially enhancing the knowledge of lactation biology, and improving infant feeding practices to meet their needs.

Exploring Impact of Probiotic-Fermented Soymilk on Dextran-Sulfate-Sodium-Induced Ulcerative Colitis via Modulating Inflammation and Gut Microbiota Profile.

SCOPE: Lactic acid bacteria with probiotic functions and their fermentation products play a role in regulating ulcerative colitis (UC). This study investigates the potential role of fermented soymilk (FSM4) rich in isoflavones on DSS-induced UC. METHODS AND RESULTS: Mice received 3% DSS and are supplemented daily once for 1 week by NFSM and FSM4. DSS usually causes intestinal inflammation and alters the gut microbiota. FSM4 intervention improves the UC-related inflammation and gut microbiota alteration. It considerably decreases pro-inflammatories such as TNF-α, IL-1ß, and IL-6 in serum and COX-2 and MPO in colon tissues and pathogenic bacteria (Escherichia-Shigella). This facilitates gut-healthy bacteria growth. These healthy bacteria negatively correlat with pro-inflammatory factors but positively associated with acetic acid, butyric acid, and propionic acid, which may act for PPAR-γ pathway activating and NF-κB p65 pathway inhibiting, lowering the risk of UC. Overall, FSM4 might alleviate UC and significantly reverse the dysbiosis of gut microbiota via the PPAR-γ activation. It could be a good alternative for developing functional food to protect against UC. CONCLUSION: FSM4 attenuates intestinal inflammation and modulates the SCFA-producing bacteria growth, which enable the PPAR-γ activation to alleviate the UC target, which could be a dietary intervention strategy for gut health.

Stem Cell-Associated Signatures Help to Predict Diagnosis and Prognosis in Ovarian Serous Cystadenocarcinoma.

Ovarian serous cystadenocarcinoma (OV) is a fatal gynecologic cancer with a five-year survival rate of only 46%. Resistance to platinum-based chemotherapy is a prevalent factor in OV patients, leading to increased mortality. The platinum resistance in OV is driven by transcriptome heterogeneity and tumor heterogeneity. Studies have indicated that ovarian cancer stem cells (OCSCs), which are chemoresistant and help in disease recurrence, are enriched by platinum-based chemotherapy. Stem cells have a significant influence on the OV progression and prognosis of OV patients and are key pathology mediators of OV. However, the molecular mechanisms and targets of OV have not yet been fully understood. In this study, systematic research based on the TCGA-OV dataset was conducted for the identification and construction of key stem cell-related diagnostic and prognostic models for the development of multigene markers of OV. A six-gene diagnostic and prognostic model (C19orf33, CBX2, CSMD1, INSRR, PRLR, and SLC38A4) was developed based on the differentially expressed stem cell-related gene model, which can act as a potent diagnostic biomarker and can characterize the clinicopathological properties of OV. The key genes related to stem cells were identified by screening the genes differentially expressed in OV and control samples. The mRNA-miRNA-TF molecular network for the six-gene model was constructed, and the potential biological significance of this molecular model and its impact on the infiltration of immune cells in the OV tumor microenvironment were elucidated. The differences in immune infiltration and stem cell-related biological processes were determined using gene set variation analysis (GSVA) and single-sample gene set enrichment analysis (ssGSEA) for the selection of molecular treatment options and providing a reference for elucidating the posttranscriptional regulatory mechanisms in OV.

Effect of Different Dietary Patterns on Macronutrient Composition in Human Breast Milk: A Systematic Review and Meta-Analysis.

The aim of this meta-analysis was to systematically review the relationships between lactation diet and the composition of mature breast milk through screening multiple databases and gray literatures, with priority given to quantitative articles published in Chinese and English. We identified 27 cross-sectional studies that included 4355 lactating women. According to these data, dietary patterns were categorized into four patterns based on the fat and protein energy supplying ratio, including rational-fat and rational-protein dietary (RR), high-fat and high-protein dietary (HH), rational-fat and high-protein dietary (RH), and high-fat and rational-protein dietary (HR). The results showed the fat content in mature milk was increased with increments of fat intake, while both the protein and lactose contents in mature milk did not increase with their intakes for lactating mothers. Among these four dietary patterns, the energy ratio of macronutrients in human milk at the RR was the closest to the estimated energy ratio for infants aged 0-6 M. In conclusion, our study represents that the rational dietary pattern should be advocated, and the irrational dietary patterns, especially high-fat and high-protein dietary patterns, should be avoided during lactation stage.

Modulation of PPARα-thermogenesis gut microbiota interactions in obese mice administrated with zingerone.

BACKGROUND: This study aimed to uncover the potential effects of zingerone (ZIN), one of the bioactive compounds in ginger, on the development of obesity as well as the mechanisms responsible for these effects in C57BL/6J mice fed with a high-fat diet (HFD). RESULTS: Supplementation with 0.2% (wt/wt) zingerone for 16 weeks significantly reduced the final body weight, liver weight, and epididymal white adipose tissue (eWAT) weight without changing the food intake of the mice when compared with the HFD group. The hyperlipidemia of HFD-fed mice was ameliorated after zingerone administration, including decreased plasma triacylglycerol (TG) and total cholesterol (TC) level. The lipid content in liver was lower and the adipocyte size in eWAT and inguinal white adipose tissue (iWAT) was smaller in HFD + ZIN-fed mice compared with HFD group. Zingerone also binds with nuclear hormone receptor peroxisome proliferator-activated receptor alpha (PPARα) with an optimal docking energy of -7.31 kJ/mol. Uncoupling protein 1 (UCP1), PPAR-γ coactivator-1α (PGC-1α), and PR domain containing 16 (PRDM16), the downstream genes of PPAR which are related to thermogenic function of adipocytes, were significantly increased in both brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) after zingerone administration, in comparison with HFD fed mice. Zingerone intake also restructured the community composition of gut microbiota. The ratio of Firmicutes to Bacteroidetes was decreased, and the relative abundance of Akkermansia_mucinphila was increased. CONCLUSION: Zingerone can attenuate obesity and related symptoms in HFD-fed mice, probably through the modulation of PPARα-thermogenesis-gut microbiota interactions. © 2022 Society of Chemical Industry.

Difference and ratio of the cross-sectional area of median nerve at the carpal tunnel and the pronator quadratus muscle in diagnosing carpal tunnel syndrome: a cross-sectional study.

Background: At present, the most commonly used diagnostic method of carpal tunnel syndrome (CTS) is based on clinical manifestations and electrophysiology, but the electrophysiology is not cheap, invasive, and lacks the presentation of peripheral nerve conditions, which is exactly the advantage of ultrasound (US). The purpose of this study was to evaluate the accuracy and effectiveness of US in the diagnosis of CTS by calculating the cross-sectional area (CSA) at the carpal tunnel and proximally at the level of the pronator quadratus muscle., and to find an appropriate index that can be used to achieve the diagnosis in a more cost-effective manner. Methods: Forty-three wrists from 35 symptomatic CTS patients and 23 wrists from 18 asymptomatic volunteers were evaluated. Diagnosis in the CTS group was based on the American Academy of Neurology clinical diagnostic criteria. The ultrasonic probe was placed at the carpal tunnel and the distal 1/3 of the pronator muscle respectively, and the carpal tunnel cross-sectional area (CSAC) and the proximal cross-sectional area (CSAP) was calculated, with a further calculation of their difference (ΔCSA) and ratio (R-CSA). Results: There was a significant difference between the 2 groups regarding mean ± standard deviation (SD) of CSAC, CSAP, ΔCSA, and R-CSA (P<0.01). The cutoff value of 12.14 mm2 for CSAC had a sensitivity and specificity of 90.7% and 100%, respectively; the cutoff value of 1.235 mm2 for R-CSA had a sensitivity and specificity of 97.67% and 95.65%, respectively; and the cutoff value of 2.035 mm2 for ΔCSA had a sensitivity and specificity of 100% and 100%, respectively. Therefore, US was found to be an effective method for the diagnosis of CTS. Receiver operating characteristic curve (ROC) analysis of all patients showed area under the curve (AUC) was 0.9778 for CSAC, 0.9949 for R-CSA and 1.000 for ΔCSA. Conclusions: US can provide reference values for the diagnosis of CTS. CSAC, ΔCSA, and R-CSA can be used for CTS diagnosis and evaluation. The ROC curve analysis showed that among the 3 values, ΔCSA was the most useful in the diagnosis of patients with CTS. ΔCSA is considered a valid diagnostic value for CTS, as its threshold of 2.04 mm2 showed the highest sensitivity and specificity.

Comparison of therapeutic efficacy of three methods to prevent re-adhesion after hysteroscopic intrauterine adhesion separation: a parallel, randomized and single-center trial.

BACKGROUND: This research aims to study the efficacy of an integrated approach to prevent and treat the recurrence of intrauterine adhesions (IUA) after hysteroscopic adhesiolysis. METHODS: A total of 96 patients diagnosed with moderate-to-severe intrauterine adhesions (IUA) in Nantong Maternal and Child Health Hospital from January 2016 to December 2019 were included in this parallel, randomized and single-center trial. Moderate (48 cases) and severe (48 cases) patients were randomly divided into three groups by a computer random generator: Group A (IUD, n=16), Group B, (Foley1w+IUD, n=16) and Group C (Foley1m+IUD, n=16). All patients received sequential treatment of estrogen and progesterone on the day of operation. Follow-up was performed at 1 and 3 months after treatment of uterine cavity, endometrial thickness, menstruation and pregnancy. Surgeons who performed the second-look and third-look hysteroscopy and postsurgical assessors were blinded to the randomization. RESULTS: In total, 96 patients (48 cases in each degree) were included in the final analysis, with 16 cases in each group. No cases were lost to follow up. The primary outcome measure was AFS score, which was significantly lower in Group C than that of women in group A and Group B at 1 month (P<0.05). Similar results were observed at 3-month follow up. In patients with moderate adhesions, the pregnancy rate in Group C (Foley1m+IUD) was higher than that in Group A and Group B (P<0.05). However, in patients with severe adhesions, there was no significant difference in the pregnancy rate among the three groups (P>0.05). There was no statistical significance in infection indicators among the three groups of moderate and severe patients (P>0.05). Postoperative complications such as uterine perforation, severe bleeding, water poisoning and intrauterine infection were not observed. CONCLUSIONS: The effect of a Foley intrauterine balloon combined with IUD in preventing re-adhesion was better than that of an IUD alone. For patients with moderate adhesion, the prolongation of placement time could prevent intrauterine re-adhesion and significantly improve the pregnancy rate with strong safety. However, for patients with severe adhesions, the prolongation of intrauterine Foley balloon placement did not better prevent intrauterine re-adhesions, improve menstruation, or improve pregnancy rates. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100046945.

Bioinformatics Analysis of Potential Therapeutic Targets and Prognostic Biomarkers amid CXC Chemokines in Ovarian Carcinoma Microenvironment.

BACKGROUND: Ovarian cancer (OC) is one of the leading lethal gynecologic cancers of women around the world. More than 70% of patients are diagnosed with stage III or IV with poor outcome. This is partly because of lacking early effective screening techniques and potential biomarkers of OC. CXC chemokines in tumor microenvironment (TME) and their interaction with relative receptors can excite the downstream signaling pathways to influence tumor progression. However, the role of CXC chemokines in OC has not been identified. METHODS: ONCOMINE, GEPIA, Kaplan-Meier plotter, cBioPortal, TIMER, Metascape, and LinkedOmics were applied in our study. RESULTS: The transcriptional levels of CXCL1/8/9/10/11/12/13/14/16/17 were significantly elevated while CXCL3 was obviously reduced in OC vs normal ovarian tissue. CXCL8/9/11/13 were correlated with clinic pathological stage. Patients with low expression of CXCL8/9/11/13 were associated with better prognosis. We also found that CXCL3 and CXC12 could be used as potential prognostic markers of OC through Kaplan-Meier plotter. Patients with high expression of CXCL3/12 had a significantly better prognosis. Their functions focus on locomotion, signaling, response to stimulus, undergoing the process of multiorganism, immune system, biological regulation, etc. The differentiated CXC chemokines mainly participate in cytokine-cytokine receptor interaction, chemokine signaling pathway, IL-17 signaling pathway, and toll-like receptor signaling pathway. Our results showed that CXC chemokines were highly correlated with infiltration of immune cells. The kinase targets of differentially expressed CXC chemokines are mainly in ATM, LYN, LCK, PLK1, FYN, CDK2, and ATR. CONCLUSIONS: Our results may provide a new insight for selecting precision biomarkers of targeted therapy of OC.

Comparative Effectiveness and Safety of High-Intensity Focused Ultrasound for Uterine Fibroids: A Systematic Review and Meta-Analysis.

Background: Uterine fibroids are common benign tumors among premenopausal women. High- intensity focused ultrasound (HIFU) is an emerging non-invasive intervention which uses the high-intensity ultrasound waves from ultrasound probes to focus on the targeted fibroids. However, the efficacy of HIFU in comparison with that of other common treatment types in clinical procedure remains unclear. Objective: To investigate the comparative effectiveness and safety of HIFU with other techniques which have been widely used in clinical settings. Methods: We searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Cumulative Index to Nursing & Allied Health Literature, Web of Science, ProQuest Nursing & Allied Health Database, and three Chinese academic databases, including randomized controlled trials (RCTs), non-RCTs, and cohort studies. The primary outcome was the rate of re-intervention, and the GRADE approach was used to interpret the findings. Results: About 18 studies met the inclusion criteria. HIFU was associated with an increased risk of re-intervention rate in comparison with myomectomy (MYO) [pooled odds ratio (OR): 4.05, 95% confidence interval (CI): 1.82-8.9]. The results favored HIFU in comparison with hysterectomy (HYS) on the change of follicle-stimulating hormone [pooled mean difference (MD): -7.95, 95% CI: -8.92-6.98), luteinizing hormone (MD: -4.38, 95% CI: -5.17-3.59), and estradiol (pooled MD: 43.82, 95% CI: 36.92-50.72)]. HIFU had a shorter duration of hospital stay in comparison with MYO (pooled MD: -4.70, 95% CI: -7.46-1.94, p < 0.01). It had a lower incidence of fever (pooled OR: 0.15, 95% CI: 0.06-0.39, p < 0.01) and a lower incidence of major adverse events (pooled OR: 0.04, 95% CI: 0.00-0.30, p < 0.01) in comparison with HYS. Conclusions: High-intensity focused ultrasound may help maintain feminity and shorten the duration of hospital stay. High-quality clinical studies with a large sample size, a long-term follow-up, and the newest HIFU treatment protocol for evaluating the re-intervention rate are suggested to be carried out. Clinical decision should be based on the specific situation of the patients and individual values.

Preparation of doxorubicin-loaded collagen-PAPBA nanoparticles and their anticancer efficacy in ovarian cancer.

BACKGROUND: The aims of this study were to prepare the collagen-poly (3-acrylamidophenylboronic acid) nanoparticles (collagen-PAPBA NPs) encapsulating doxorubicin (DOX) and research their anticancer efficacy in ovarian cancer. METHODS: Collagen-PAPBA NPs were prepared, and their morphology and stability morphology were observed by transmission electron microscopy (TEM) and dynamic light scattering system (DLS). Preparation of doxorubicin-loaded Collagen-PAPBA NPs (DOX-loaded NPs) were then prepared, and the drug-loading content, encapsulation efficiency, and in vitro drug-release profiles were calculated. The morphology of DOX-loaded NPs was also observed by DLS, in vitro cytotoxicity to A2780 cells was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, in vitro antitumor activity on A2780 cells was observed by immunofluorescence, and in vivo antitumor activity was assessed using an experimental BALB/c mice tumor model. RESULTS: DOX-encapsulating collagen-PAPBA NPs were successfully prepared with mediation by biomolecule. The average hydrodynamic diameter of collagen-PAPBA NPs as measured by DLS was about 79 nm, with a homogeneous distribution of size. TEM revealed that nanoparticles were well-dispersed, spherical, and a roughly uniform 75 nm in size. Collagen-PAPBA NPs were quite stable in a wide range of pH and temperature conditions and associated with the concentration of glucose. DLS revealed that the average hydrodynamic diameter of DOX-loaded NPs was about 81.3 nm, with homogeneous distribution of size. TEM revealed that drug-loaded nanoparticles were spherical, well-dispersed, and gad a roughly uniform size of 79 nm. The proportion of DOX loaded into the nanoparticles was 10%, while the encapsulating efficiency was 97%. The result of the releasing test showed that the drug-loaded nanoparticles, as carriers for DOX, had a good sustained-release effect. The cell toxicity experiment showed that the blank NPs had no cytotoxicity to A2780 cells, and that the drug-loaded NPS had good a sustained-release function. They may thus have potential toxic-reducing side effects. CONCLUSIONS: Under the same doses, the drug-loaded NP had a superior inhibitory effect to free DOX on the growth of human ovarian cancer.

CircRNA hsa_circRNA_0000069 promotes the proliferation, migration and invasion of cervical cancer through miR-873-5p/TUSC3 axis.

BACKGROUND: Cervical cancer (CC) is the second leading cause of cancer deaths in women worldwide, still lacking effective biomarkers and therapies for diagnosis and treatment. CircRNAs are a class of endogenous RNAs that regulate gene expression through interacting with miRNAs, implicating in the progression of cancers. Yet the roles of circRNAs in CC are not fully characterized. METHODS: Fifty pairs of tumor and adjacent normal tissues from CC patients, as well as four CC cell lines and a normal human cervical epithelial cell line were subjected to qRT-PCR assay to assess the mRNA levels of hsa_circ_0000069. CCK-8 and colony formation assays were conducted to detect the proliferation of CC cells. Transwell assay was used to evaluate the migration and invasion capabilities of CC cells. RNA pull-down and luciferase assays were used to determine the interaction between hsa_circ_0000069 and miR-873-5p. A xenograft model of CC was established to verify the in vivo function of hsa_circ_0000069 in CC progression. RESULTS: We firstly demonstrated that hsa_circ_0000069 was significantly upregulated and closely related to the lymph node metastasis, and poor prognosis of CC patients. Besides, hsa_circ_0000069 promoted CC cell proliferation, migration, and invasion. The knockdown of hsa_circ_0000069 also inhibited CC tumor growth in vivo. Mechanically, we revealed that hsa_circ_0000069 functioned as an oncogene in CC, which is the sponge of miR-873-5p to facilitate the TUSC3 expression, consequently promoting CC progression. CONCLUSION: We demonstrated a critical hsa_circ_0000069-miR-873-5p-TUSC3 function network involved in the CC progression, which provides mechanistic insights into the roles of CircRNAs in CC progression and a promising therapeutic target for CC treatment.

High neuropilin and tolloid-like 1 expression associated with metastasis and poor survival in epithelial ovarian cancer via regulation of actin cytoskeleton.

Abnormal expression of neuropilin and tolloid-like 1 (NETO1) has been detected in some human carcinomas. However, the expression of NETO1 and the underlying mechanism in epithelial ovarian cancer (EOC) remain unknown. In this study, we found that a higher NETO1 expression in EOC tissue samples compared to normal ovarian tissue samples was significantly correlated with worse overall survival. Additionally, Cox regression analysis suggested that NETO 1 was independently associated with overall survival. NETO1 overexpression enhanced the EOC cells' migration and invasion capability in vitro via regulation of actin cytoskeleton. Mechanistically, silencing NETO1 reduced the expression of ß-tubulin, F-actin and KIF2A. In conclusion, our results demonstrated the critical role of NETO1 in EOC invasion, and therapies aimed at inhibiting its expression or activity might significantly control EOC growth, invasion and metastatic dissemination.

Methylation of PLIN5 is a crucial biomarker and is involved in ovarian cancer development.

BACKGROUND: PLIN5 is abnormally expressed in many forms of tumors, but its activity and methylation status in human ovarian cancer (OC) have yet to be elucidated. METHODS: RNA sequencing data (RNA-seq) were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database. Differentially expressed genes (DEGs) were identified, and then PLIN5 gene was selected for further study. Expression and methylation levels of PLIN5 were detected by qPCR, western blot, immunohistochemical, and MSP analysis. Moreover, colony formation, transwell, and cell apoptosis assays were employed to explore the abilities of cell proliferation, migration, invasion, and apoptosis, respectively. Furthermore, PLIN5's function on tumorigenesis was determined by in vivo experiments. RESULTS: We found that PLIN5 was downregulated in OC tissues by using qPCR, western blot, and immunohistochemical analyses, and MSP also exhibited that PLIN5 was hypermethylated in OC tissues. The expression level of PLIN5 could be restored after treatment with 5-Aza-dC. Furthermore, we found that demethylated PLIN5 could suppress cell proliferation, migration, and invasion of OC, and increase cell apoptosis. Moreover, xenograft experiments showed that demethylated PLIN5 could suppress tumor growth. CONCLUSIONS: Our findings suggest that the expression level of PLIN5 is regulated by methylation, and in OC, PLIN5 can act as a tumor suppressor.

microRNA-132 inhibits the proliferation, migration, and invasion of ovarian cancer cells by regulating CT10 oncogenic gene homolog II-related signaling pathways.

BACKGROUND: Despite a large amount of evidence showing the involvement of microRNA-132 (miR-132) in the occurrence and prognosis of many different types of cancer, the role of miR-132 in ovarian cancer and its potential molecular mechanism have yet to be fully explained. METHOD: We studied the biological function and molecular mechanism of miR-132 in ovarian cancer cell lines and clinical tissue samples using quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot, Luciferase reporter assay, CCK8 test, colony formation test, and scratch and Transwell assays. RESULTS: The expression level of miR-132 was significantly reduced in ovarian cancer cell lines and clinical tissue samples. When the level of miR-132 was increased, the proliferation, colony-forming, migration, and invasion abilities of ovarian cancer cells were significantly inhibited. We found that miR-132 inhibits the expression of transcription factor CT10 Oncogenic Gene Homologue II (CRKII) through specific targeting of mRNA 3'-UTR. We also observed a significant increase in CRKII expression in ovarian cancer. Notably, CRKII expression was negatively correlated with miR-132 expression in clinical ovarian cancer tissue. Down-regulation of CRKII had a similar inhibitory effect on miR-132 overexpression in ovarian cancer cells, while excessive expression of CRKII reversed the inhibitory effect mediated by the excessive expression of miR-132. CONCLUSIONS: miR-132 inhibits the proliferation, invasion, and migration abilities of ovarian cancer cells through targeting CRKII.

Overexpression of KIF2A is Suppressed by miR-206 and Associated with Poor Prognosis in Ovarian Cancer.

BACKGROUND/AIMS: This study aimed to investigate the expression and prognostic value of kinesin family member 2A (KIF2A) and the suppression effects of microRNA-206 (miR-206) on KIF2A in ovarian cancer. METHODS: Ovarian cancer tissues from patients and ovarian cancer cell lines (A2780 and SKOV3) were used in this study. miR-206 mimics and control were transiently transfected into cells. RT-qPCR was performed to detect KIF2A mRNA and miR-206 expression levels, Western blot was performed to detect KIF2A protein levels, Dual-Luciferase Reporter Assay was used to examine the inhibition effects of miR-206 on KIF2A mRNA, immunohistochemical staining was used to examine the expression of KIF2A in tissue sections. CCK-8, transwell and Annexin-V-FITC/Propidium Iodide staining with flow cytometry were used to detect the cell proliferation, migration/invasion, and apoptosis respectively. RESULTS: Our study explored the expression profiles of KIF2A and miR-206 in the patients with ovarian cancer. We found that overexpression of KIF2A was associated with a poor prognosis in ovarian cancer. We also found that KIF2A mRNA contains two target sites for miR-206 binding and confirmed that miR-206 directly suppresses KIF2A; inhibits ovarian cancer cell proliferation, migration, and invasion; and induces apoptosis. CONCLUSION: The results suggest KIF2A could serve a valuable prognostic indicator in ovarian cancer and provide a rationale for treatment of ovarian cancer by targeting KIF2A via miR-206.

Decreased Eph receptor­A1 expression is related to grade in ovarian serous carcinoma.

Eph receptor­A1 (EphA1) was the first member of the erythropoietin producing hepatocellular carcinoma (Eph) family of receptor tyrosine kinases. Although the roles of EphA1 in the tumorigenesis of various human cancers have been investigated, few studies have focused on ovarian carcinoma. The present study aimed to explore the profile of EphA1 expression in ovarian carcinomas, to analyzed the association between EphA1 expression and clinicopathologic parameters, and to investigate the roles of overexpressed EphA1 in ovarian cancer cells. EphA1 protein was detected in ovarian cancer cell lines and in a set of formalin­fixed tissues, including normal fallopian tube, ovarian benign serous cystadenoma, borderline serous tumors and serous carcinoma. Ovarian cancer cell lines HO8910 and A2780 were transiently transfected with EphA1­pCMV6­GFP plasmid, and the proliferation and apoptosis of cells were measured. The association between EphA1 expression and clinicopathological parameters was statistically analyzed. EphA1 expression was negative in HO8910 and weakly positive in A2780 cells. The proliferation rate was significantly reduced in ovarian cancer cells after transfection with EphA1 plasmid compared with cells transfected with mock plasmid or untreated cells, but no obvious alteration in apoptosis was detected among these groups. EphA1 expression was positively detected in all normal fallopian tubes (10/10, 100%) and ovarian benign serous cystadenomas (12/12, 100%) as well as in some borderline serous tumors (9/15, 60%) and ovarian serous carcinomas (33/76, 43.42%). EphA1 expression was associated with grade of ovarian serous carcinomas, with loss of EphA1 more often observed in high­grade tumors (P=0.016) and high Ki67 index tumors (P=0.007). These data suggest that EphA1 might be a useful marker for distinguishing low grade from high­grade ovarian serous carcinoma.

Synthesis of methylprednisolone loaded ibuprofen modified dextran based nanoparticles and their application for drug delivery in acute spinal cord injury.

To improve the therapeutic efficacy of spinal cord injury (SCI), the methylprednisolone was incorporated into nanoparticles based on the ibuprofen modified dextran. The ibuprofen modified dextran was synthesized using a direct esterification linkage between the carboxylic acids of hydrophobic drug and the hydroxyl groups of the polymer backbone. The morphology of methylprednisolone loaded nanoparticles was evaluated by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The therapeutic efficacy of the prepared nanoparticles on the acute SCI model rats was assessed. It is demonstrated that methylprednisolone loaded ibuprofen modified dextran based nanoparticles (MP-loaded NPs) could promote the recovery of neurological deficits, enhance growth of neurons, decrease degeneration of injuried neurons and reduce the tissue tumor necrosis factor alpha (TNF-α) levels significantly in the SCI rats. Subsequently, the study indicates that synthesis of methylprednisolone loaded ibuprofen modified dextran based nanoparticles has a great potential in the synergetic effect treatment for spinal cord injury and nanoparticles based drug delivery system will become a powerful weapon of human conquest of disease.