AEBP1 upregulation contributes to cervical cancer progression by facilitating cell proliferation, migration, and invasion.

BACKGROUND: Aberrant expression of adipocyte enhancer-binding protein 1 (AEBP1) has been demonstrated to be involved in the tumorigenesis and progression of numerous cancers. This study was aimed to investigate the mechanism of AEBP1 in the development of cervical cancer. METHODS: The expression of AEBP1 in cervical cancer was assessed by immunohistochemistry. The function of AEBP1 on cell proliferation, migration, and invasion was determined by methyl thiazolyl tetrazolium assay, colony formation, and transwell assay. The activation of related signaling pathway was determined by western blot. The bioinformatics analysis was performed by Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. RESULTS: Higher protein expression of AEBP1 was observed in patients with cervical cancer. Overexpressed AEBP1 promoted cell proliferation, migration, and invasion abilities in cervical cancer cells. Moreover, the research manifested that AEBP1 activated the phosphorylation of STAT3. GO and KEGG analysis showed that genes positively related to AEBP1 were highly enriched in functions like epithelial cell proliferation, muscle cell migration, myoblast migration, smooth muscle tissue development, ECM-receptor interaction, transcriptional misregulation in cancer, and proteoglycans in cancer. While genes negatively related to AEBP1 were associated with immunity, including inflammatory response, external-stimulus response, neutrophil, granulocyte, and macrophage chemotaxis. CONCLUSIONS: This study suggested that AEBP1 acts as an oncogened and might be a potential therapeutic target for the treatment of cervical cancer.

Missed Spontaneous Heterotopic Pregnancy: A Case Report of a Ruptured Tubal Pregnancy after Induced Abortion.

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Polymyxin E biomineralized and doxorubicin-loaded gold nanoflowers nanodrug for chemo-photothermal therapy.

Gold nanoparticles are a kind of good photothermal agents. However, gold nanoparticle photothermal agents have low photothermal conversion efficiency and low tumor inhibiting ability. To overcome these problems, polymyxin E (PE) biomineralized and doxorubicin-loaded gold nanoflowers (DOX-SH@AuNFs) nanodrug was synthesized by the green synthesis method using the biological antimicrobial peptide PE as a stabilizer and grower of crystal seed, and doxorubicin-thiol (DOX-SH) was further loaded on the gold nanoparticles through the Au-S bond. The final DOX-SH@AuNFs displayed a wide absorption band in the UV-Vis spectra, and their photothermal conversion efficiency was 33.9%. Furthermore, the inhibition rate of DOX-SH@AuNFs on A549 cells was as high as 80.1% under the irradiation of near-infrared light at 808 nm. The tumor inhibition rate of DOX-SH@AuNFs was as high as 87.81% in vivo experiments. The high tumor suppression rate was attributed to the high photothermal conversion ability of DOX-SH@AuNFs and the delivery of doxorubicin. Taken together, the method of preparing DOX-SH@AuNFs provides a new idea for the treatment of cancer by photothermal therapy and chemotherapy synergistic system.

Analysis of risk factors for cesarean scar diverticulum: A STROBE-compliant case-control study.

ABSTRACT: The purpose of this study was to explore the relevant factors that affect the risk of cesarean scar diverticulum (CSD).A retrospective, case-control study was designed among women with a history of cesarean section (CS) who were admitted in Zhejiang Tongde Hospital from January 2017 to December 2019. Women with missing information were excluded. The basic clinical characteristics and the risk factors for CSD were assessed using univariate analysis and multivariate logistic regression analysis.A total of 216 women were analyzed, including 87 patients with CSD and 129 cases without CSD as control. Significant differences in number of CS, trial of labor (elective or urgent CS), CS interval, uterine position, intraoperative hemorrhage, and dysmenorrhea between CSD group and control group (P < .05). Multivariate logistic regression analysis showed that number of CS, trial of labor, interval of CS, and uterine position were independent risk factors of CSD.In women with a history of CS, multiple cesarean deliveries, elective CS, cesarean interval of less than 5 years, and retroflexed position of the uterus may be associated with an elevated risk of CSD.

CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation.

Hematopoietic stem and progenitor cell (HSPC) formation and lineage differentiation involve gene expression programs orchestrated by transcription factors and epigenetic regulators. Genetic disruption of the chromatin remodeler chromodomain-helicase-DNA-binding protein 7 (CHD7) expanded phenotypic HSPCs, erythroid, and myeloid lineages in zebrafish and mouse embryos. CHD7 acts to suppress hematopoietic differentiation. Binding motifs for RUNX and other hematopoietic transcription factors are enriched at sites occupied by CHD7, and decreased RUNX1 occupancy correlated with loss of CHD7 localization. CHD7 physically interacts with RUNX1 and suppresses RUNX1-induced expansion of HSPCs during development through modulation of RUNX1 activity. Consequently, the RUNX1:CHD7 axis provides proper timing and function of HSPCs as they emerge during hematopoietic development or mature in adults, representing a distinct and evolutionarily conserved control mechanism to ensure accurate hematopoietic lineage differentiation.

KNDC1 Is a Predictive Marker of Malignant Transformation in Borderline Ovarian Tumors.

BACKGROUND: Few screening markers for malignant transformation in borderline ovarian tumors (BOT) have been clearly established. The kinase noncatalytic C-lobe domain containing 1 (KNDC1), a brain-specific Ras guanine nucleotide exchange factor, negatively regulates dendrite growth. However, the biological role and underlying mechanism of KNDC1 in human cancers, including ovarian cancer (OC), remain unknown. METHODS: Gene chip screening was used to detect the expression of KNDC1 mRNA in normal ovarian tissues, BOT tissues, and OC tissues. And results were further validated by RT-qPCR, Western blotting and immunohistochemistry. KNDC1 overexpression and knockdown ovarian cancer cells were established to study the possible pathways that KNDC1 was involved. The effects of KNDC1 on the malignant behaviors of ovarian tumors were also investigated both in vitro and in vivo. RESULTS: We observed that the expression of KNDC1 mRNA and KNDC1 protein in OC was significantly downregulated compared with BOT. Subsequent investigation revealed that knockdown of KNDC1 enhanced the proliferation of ovarian cancer cells in vitro via induction of ERK1/2 phosphorylation, whereas reinforcing the expression of KNDC1 attenuated the ERK1/2 activity. Similarly, knockdown of KNDC1 also promoted cell proliferation in vivo. Survival analysis showed that lower KNDC1 predicted a poor progression-free survival (PFS) for patients. CONCLUSION: Collectively, we conclude that KNDC1 might function as a tumor suppressor in ovarian tumors, inhibiting the proliferation of ovarian cells by suppressing ERK1/2 activity and hindering the malignant transformation of BOT.

Ultra-small and biocompatible platinum nanoclusters with peroxidase-like activity for facile glucose detection in real samples.

The highly sensitive glucose detection based on the peroxidase-like properties of nanoclusters has been gained great interest. In this work, Pericarpium Citri Reticulatae polysaccharide (PCRP) stabilized platinum nanoclusters (Pt-PCRP NCs) were prepared by a green method in which potassium tetrachloroplatinate and PCRP were simply mixed without addition of other agents. Platinum nanoclusters (Pt NCs) had ultra-small size of 1.26 ± 0.34 nm. The hydrodynamic size of Pt-PCRP NCs was 29.7 nm, and zeta potential of which was -12.0 mV. Pt-PCRP NCs showed high biocompatibility toward HeLa cells and red blood cells. In addition, Pt-PCRP NCs catalyzed the decomposition of H2O2 to produce •OH, which further oxidized colorless 3,3'5,5'-tetramethylbenzidine (TMB) to blue oxidized 3,3',5,5'-tetramethylbenzidine (oxTMB), exhibiting peroxidase-like property. The kinetics followed the Michaelis-Menten equation. More importantly, the colorimetric method for glucose detection using Pt-PCRP NCs had high selectivity and low detection limit for 0.38 µM. The established method based on Pt-PCRP NCs was used to precisely detect glucose detection in human serum, saliva, and sweat. Taken together, the prepared ultra-small and biocompatible Pt-PCRP NCs have good potential glucose applications in clinical diagnosis in the future.

Tumor-Associated Macrophages (TAMs): A Critical Activator In Ovarian Cancer Metastasis.

Tumor-associated macrophages (TAMs) that appear in every stage of cancer progression are usually tumor-promoting cells and are present abundantly in the tumor-associated microenvironment. In ovarian cancer, the overall and intratumoral M1/M2 ratio is a relatively efficient TAM parameter for predicting the prognosis of patients, especially for serous tissue type cancer. TAMs exhibit immunological checkpoint modulators, such as the B7 family and programmed death-ligand 1 (PD-L1), and play a key role in the development, metastasis and invasion of ovarian cancer, but the underlying mechanism is barely understood. Ovarian cancer is a severe gynecological malignancy with high mortality. Ovarian cancer-associated death can primarily be attributed to cancer metastasis. The majority of patients are diagnosed with wide dissemination in the peritoneum and omentum, limiting the effectiveness of surgery and chemotherapy. In addition, unlike other well-documented cancers, metastasis through vasculature is not a usual dissemination pathway in ovarian cancer. This review sheds light on TAMs and the main process and mechanism of ovarian cancer metastasis.

Identification of key biomarkers associated with development and prognosis in patients with ovarian carcinoma: evidence from bioinformatic analysis.

BACKGROUND: Ovarian cancer (OC) is the deadliest cause in the gynecological malignancies. Most OC patients are diagnosed in advanced stages with less than 40% of women cured. However, the possible mechanism underlying tumorigenesis and candidate biomarkers remain to be further elucidated. RESULTS: Gene expression profiles of GSE18520, GSE54388, and GSE27651 were available from Gene Expression Omnibus (GEO) database with a total of 91 OC samples and 22 normal ovarian (OV) tissues. Three hundred forty-nine differentially expressed genes (DEGs) were screened between OC tissues and OV tissues via GEO2R and online Venn software, followed by KEGG pathway and gene ontology (GO) enrichment analysis. The enriched functions and pathways of these DEGs contain male gonad development, cellular response to transforming growth factor beta stimulus, positive regulation of transcription from RNA polymerase II promoter, calcium independent cell-cell adhesion via plasma membrane cell adhesion molecules, extracellular matrix organization, pathways in cancer, cell cycle, cell adhesion molecules, PI3K-AKT signaling pathway, and progesterone mediated oocyte maturation. The protein-protein network (PPI) was established and module analysis was carried out using STRING and Cytoscape. Next, with PPI network analyzed by four topological methods in Cytohubba plugin of Cytoscape, 6 overlapping genes (DTL, DLGAP5, KIF15, NUSAP1, RRM2, and TOP2A) were eventually selected. GEPIA and Oncomine were implemented for validating the gene expression and all the six hub genes were highly expressed in OC specimens compared to normal OV tissues. Furthermore, 5 of 6 genes except for DTL were associated with worse prognosis using Kaplan Meier-plotter online tool and 3 of 6 genes were significantly related to clinical stages, including RRM2, DTL, and KIF15. Additionally, cBioPortal showed that TOP2A and RRM2 were the targets of cancer drugs in patients with OC, indicating the other four genes may also be potential drug targets. CONCLUSION: Six hub genes (DTL, DLGAP5, KIF15, NUSAP1, RRM2, and TOP2A) present promising predictive value for the development and prognosis of OC and may be used as candidate targets for diagnosis and treatment of OC.

miR-291b-3p mediated ROS-induced endothelial cell dysfunction by targeting HUR.

Endothelial dysfunction is an early marker of atherosclerosis. Previous studies have indicated that microRNA (miR)­291b­3p regulates the metabolism of lipids and glucose in the liver via targeting adenosine monophosphate­activated kinase α1 and transcription factor p65. The present study investigated whether miR­291b­3p mediated H2O2­mediated endothelial dysfunction. The level of apoptosis of EOMA mouse endothelial cells was analyzed by terminal deoxynucleotidyl­transferase­mediated dUTP nick end labelling staining. The mRNA levels of miR­291b­3p, intercellular adhesion molecule­1 (ICAM­1) and vascular adhesion molecule­1 (VCAM­1) were determined by quantitative polymerase chain reaction. The level of phosphorylated extracellular signal­regulated kinase, and levels of B­cell lymphoma 2 (Bcl­2)­associated X protein and Bcl­2 protein were detected by western blot analysis. The treatment of H2O2 induced the apoptosis and increased the mRNA levels of miR­291b­3p, ICAM­1 and VCAM­1 in EOMA cells. It was also demonstrated that the overexpression of miR­291b­3p promoted EOMA cell apoptosis and dysfunction. In contrast, the downregulation of miR­291b­3p rescued the effect of H2O2 on EOMA cell dysfunction. In addition, Hu antigen R (HuR) was identified as a target gene of miR­291b­3p in EOMA cells. The overexpression of HuR reversed the endothelial dysfunction induced by miR­291b­3p mimics. The present study provides novel insight into the critical role of miR­291b­3p on the endothelial dysfunction induced by H2O2. miR­291b­3p may mediate H2O2­induced endothelial dysfunction via targeting HuR.

Advances of exosome in the development of ovarian cancer and its diagnostic and therapeutic prospect.

Ovarian cancer is the leading cause of female gynecological cancer mortality. Most patients with ovarian cancer are diagnosed with advanced stage because of lack of early symptoms, physical signs, and sensitive tumor biomarkers. The standard treatment includes cytoreductive surgery and platinum-based chemotherapy (usually platinum combined with paclitaxel). Despite that postoperative adjuvant chemotherapy prolongs survival time, most patients go through relapse within 6-12 months after the treatment. Thus, elucidating the molecular mechanism in cancer development is essential to promote early diagnosis and novel treatments. The role of exosome has been highlighted in multiple research fields in recent years. Exosome has been described as nano-sized vesicle secreted by multiple mammalian cell types, carrying cargos like proteins, miRNAs, mRNAs, and lipids. It participates in the formation of tumor microenvironment and the development of tumorigenesis and drug resistance in ovarian cancer. Meanwhile, it may also play a pivotal role in diagnosis, efficacy evaluation, and prognosis. Besides, studies show that exosome and its processed products have promising value in ovarian cancer treatment. The aim of the current review is to describe the characteristics of exosome in ovarian cancer, especially focusing on its role in immune modulation and drug resistance, hoping to provide new information on its implications in cancer diagnosis and treatment.

LINC01088 inhibits tumorigenesis of ovarian epithelial cells by targeting miR-24-1-5p.

The roles of long non-coding RNAs (lncRNAs), a class of long non-protein-coding RNAs, in the tumorigenesis of ovarian epithelial cells remain unknown. In this study, we discovered that the expression of long intergenic non-coding RNA 1088 (LINC01088) was clearly reduced in benign epithelial ovarian tumor tissues compared to matched normal ovarian tissues. This was shown by global cDNA gene chip scanning and real-time qPCR, and validated in 42 clinical specimens. Furthermore, we found that LINC01088 inhibited the growth of ovarian cancer xenografts in nude mice. Correlation analysis between LINC01088 and mircoRNAs (miRNAs) conducted using primary clinical samples and RNA co-precipitation experiments revealed that miR-24-1-5p was one of the targets of LINC01088. Overexpression of miR-24-1-5p facilitated cell proliferation both in vitro and in vivo, however, LINC01088 could partially reverse the cell proliferation induced by miR-24-1-5p. Finally, we demonstrated that p21 activated kinase 4 (PAK4) was one of the downstream key targets of miR-24-1-5p by luciferase reporter assay and Western blotting; and our results showed a remarkable decrease in cell proliferation after overexpression of PAK4. We conclude that LINC01088 might function as a tumor suppressor, inhibiting the tumorigenesis of ovarian epithelial cells through LINC01088/ miR-24-1-5p/ PAK4 axis.

Analysis of the Relationship Between ADIPOR1 Variants and the Susceptibility of Chronic Metabolic Diseases in a Northeast Han Chinese Population.

OBJECTIVE: Shared genetic variants in ADIPOR1 have been identified as closely related to coronary artery disease (CAD), type 2 diabetes (T2D), and T2D with CAD susceptibility, suggesting that these variants are strong candidates for the common soil hypothesis. Therefore, it is essential to analyze the relationship between ADIPOR1 variants and the susceptibility to CAD, T2D, and T2D with CAD in other populations. MATERIALS AND METHODS: A case-control study was conducted which included three case cohorts [CAD (n = 316), T2D (n = 295), T2D with CAD (n = 302)], and a control cohort (n = 268) from a population in northeast China. Six ADIPOR1 single-nucleotide polymorphisms were genotyped by high-resolution melting and polymerase chain reaction-restriction fragment length polymorphism. RESULTS: We confirmed that the shared variant, rs3737884*G, in ADIPOR1 is associated with CAD, T2D, and T2D with CAD (p-value range: 6.54E-6-1.82E-5, odds ratio [OR] range: 1.770-1.844) and that rs16850797*C is associated with T2D and T2D with CAD (p-value range: 0.001-0.001, OR range: 1.529-1.571). We also found that a novel shared variant, rs7514221*C, is associated with an increased susceptibility to CAD, T2D, and T2D with CAD (p-value range: 0.002-0.004, OR range: 1.194-2.382) in this population. CONCLUSIONS: ADPOR1 variants, rs3737884*G and rs7514221*C, may be shared risk factors associated with CAD, T2D, and T2D with CAD in a population of northeast China.