Circulating inflammatory cytokines and hypertensive disorders of pregnancy: a two-sample Mendelian randomization study.

Background: Hypertensive disorders of pregnancy (HDP) pose a significant risk to maternal and fetal well-being; however, the etiology and pathogenesis of HDP remain ambiguous. It is now widely acknowledged that inflammatory response and the immune system are closely related to HDP. Previous research has identified several inflammatory cytokines are associated with HDP. This study applied Mendelian randomization (MR) analysis to further assess causality. Methods: Patients with HDP who participated in the MR analysis presented with four types of HDP: pre-eclampsia or eclampsia (PE); gestational hypertension (GH); pre-existing hypertension complicating pregnancy, childbirth and the puerperium (EH); and pre-eclampsia or poor fetal growth (PF). A two-sample MR analysis was used to analyze the data in the study. The causal relationship between exposure and outcome was analyzed with inverse variance weighting (IVW), MR Egger, weighted median, weighted mode, and simple mode methods, where IVW was the primary method employed. Results: Our MR analysis demonstrated a reliable causative effect of Interleukin-9 (IL-9) and macrophage migration inhibitory factor (MIF) on reducing HDP risk, while macrophage inflammatory protein 1-beta (MIP1b), Interleukin-13 (IL-13), and Interleukin-16 (IL-16) were associated with promoting HDP risk. Conclusions: This study demonstrated that IL-9, MIF, MIP1b, IL-13, and IL-16 may be cytokines associated with the etiology of HDP, and that a number of inflammatory cytokines are probably involved in the progression of HDP. Additionally, our study revealed that these inflammatory cytokines have causal associations with HDP and may likely be potential therapeutic targets for HDP.

Long non-coding RNA ASB16-AS1 enhances cell proliferation, migration and invasion via functioning as a ceRNA through miR-1305/Wnt/ß-catenin axis in cervical cancer.

BACKGROUND: Cervical cancer (CC) is one of the most common cancers in women. Long non-coding RNAs (lncRNAs) have been proposed as therapeutic targets in CC. Hence, the present study evaluated the effect of ASB16-AS1 on CC via regulating miR-1305. METHODS: Differentially expressed lncRNAs associated with CC were screened using bioinformatics database. The expression of ASB16-AS1 and miR-1305 were measured by qRT-PCR in CC tissues and CC cells. Cell proliferation was assessed by CCK-8 and colon formation assays. Cell abilities of migration and invasion were detected by Transwell migration and invasion assays. Luciferase report assays were used to explore the correction between ASB16-AS1, miR-1305 and Wnt2 in CC. Western blot assay detect the activity of Wnt/ß-catenin pathway. The xenograft tumor in nude mice was observed to evaluate tumor formation in vivo. RESULTS: In our study, we showed that the expression of ASB16-AS1 was increased while miR-1305 reduced was re in CC. Clinically, ASB16-AS1 and miR-1305 were correlated with poor-associated clinicopathological features of CC patients. Knockdown of ASB16-AS1 reduced CC cells proliferation, migration and invasion abilities by regulating miR-1305 in vitro and in vivo. Moreover, miR-1305 was directly bound to ASB16-AS1 and Wnt2, regulated their expression negatively. Western blot assays showed that ASB16-AS1 functioned as an oncogene by Wnt/ß-catenin pathway. CONCLUSIONS: This study reveals that ASB16-AS1 promotes cell proliferation, migration, invasion via binding miR-1305 with Wnt2, and enhancing the Wnt/ß-catenin pathway. ASB16-AS1 may play a new therapeutic target for CC.

MicroRNA-23a depletion promotes apoptosis of ovarian cancer stem cell and inhibits cell migration by targeting DLG2.

Ovarian cancer (OC) is xenogeneic that is influenced by many generated factors related to epigenetic factors to accelerate tumor metastasis. This study was conducted with the objective of investigating the effect of microRNA-23a-3p (miR-23a) on the biological characteristics of OC stem cells by targeting discs large homolog 2 (DLG2). OC-related differentially expressed genes were screened by microarray-based gene expression analysis, after which a list of miRNAs that regulate the genes was predicted. In total, 50 patients diagnosed with OC were enrolled in this study. DLG2 positive protein expression was measured in OC tissues. The interaction between DLG2 and miR-23a was predicted and analyzed through luciferase activity measurement. With the intervention of miR-23a and/or DLG2 expression in OC stem cells, the expression of miR-23a, DLG2, Bax, Bcl-2, Oct-4, and Nanog was determined. Afterward, different cell experiments were conducted to examine the regulation effect of miR-23a in OC stem cells. Tumor formation in vivo was also evaluated in nude mice. DLG2 had low expression in OC. The results showed that there was a decrease in the expression of Bcl-2, Oct-4, and Nanog, while DLG2 and Bax were increased as a result of miR-23a depletion. In addition, when miR-23a was suppressed, cell viability, migration, invasion, cloning, and renewal abilities of OC stem cells were decreased, while apoptosis ability was enhanced. As a target gene of miR-23a, DLG2 downregulation reversed the suppressive function of miR-23a in the inhibition of OC development. Finally, in vivo experiment verified that miR-23a downregulation restrained the tumor growth in OC stem cells. In conclusion, our findings suggested that the inhibition of miR-23a results in the suppression of OC progression by releasing DLG2, which provides new understanding on the potential therapeutic effect of miR-23a inhibition in OC patients.

Long non-coding RNA CCAT2 promotes epithelial-mesenchymal transition involving Wnt/ß-catenin pathway in epithelial ovarian carcinoma cells.

Long non-coding RNA colon cancer-associated transcript 2 (CCAT2) is dysregulated in a variety of types of human cancer. However, the role of CCAT2 in epithelial ovarian carcinoma (EOC) remains largely unknown. The aim of this study is to investigate the effect of CCAT2 on epithelial-mesenchymal transition (EMT) and related molecular mechanisms in epithelial ovarian cancer cells. In the current paper, we found that CCAT2 was significantly upregulated in EOC SKOV3, A2780 and HO8910 cell lines compared with the normal ovarian epithelial HUM-CELL-0088 cell line. Functional assays demonstrated that the knockdown of CCAT2 inhibited migration and invasion of EOC cells in vitro. Moreover, our results showed that silencing CCAT2 inhibited EMT by the upregulation of epithelial cadherin and downregulation of neural cadherin, zinc finger protein SNAI and Twist-related protein 1 in SKOV3 and A2780 cell lines. But, that was reversed by the treatment with lithium chloride (LiCl), by which the canonical Wnt/ß-catenin pathway could be activated. In addition, we further investigated the role of CCAT2 in the modulation of Wnt/ß-catenin signaling pathway. Our results revealed that knockdown of CCAT2 inhibited the expression of ß-catenin and the activity of T-cell factor/lymphoid enhancer factor, acting as a key transcription factor of Wnt signaling pathway. Collectively, these results indicate that CCAT2 may promote EMT, at least partly through Wnt/ß-catenin signaling pathway in EOC cells. Thus, CCAT2 might play a critical role in EOC progression and serve as a valuable target for the treatment of ovarian cancer.

Silencing CCAT2 inhibited proliferation and invasion of epithelial ovarian carcinoma cells by regulating Wnt signaling pathway.

Long non-coding RNA CCAT2 (colon cancer-associated transcript 2) is dysregulated in varieties of human tumors. However, the role of CCAT2 in epithelial ovarian carcinoma (EOC) is not yet known clearly. The aim of this study is to investigate the effects of CCAT2 on proliferation and invasion of EOC cells and the potential mechanisms by which CCAT2 functions. In the present paper, we found that knockdown of CCAT2 impaired cell proliferation and invasion in vitro. Furthermore, we also studied the role of CCAT2 in the modulation of Wnt/ß-catenin signaling pathway. Our results showed that knockdown of CCAT2 inhibited the expression of ß-catenin and the activity of TCF/LEF (T-cell factor/lymphoid enhancer factor) acting as a key transcription factor of Wnt/ß-catenin signaling pathway. In addition, we found that silencing CCAT2 down-regulated the expression of c-MYC and MMP-7. But, that was reversed by the treatment with LiCl (lithium chloride) which could activate canonical Wnt/ß-catenin signaling pathway. Taken together, these results indicate that CCAT2 may promote ovarian cancer progression, at least partly, through Wnt/ß-catenin signaling pathway. Thus, CCAT2 might represent a novel therapeutic target for ovarian cancer.

[Study on the status and related socio-psychological factors of maternal depression among high-risk pregnancy women in Harbin city].

OBJECTIVE: This study aimed to investigate the depression status among high-risk pregnancy women, and to analyze its relevant social and psychological factors. METHODS: A total of 42 high-risk pregnancy women and 40 normal pregnancy women in a teaching hospital in Harbin city were followed up at time points of 32 - 36 weeks pregnancy, one week before labor, one week postpartum, and six weeks postpartum, respectively. During follow-up, the basic situation, social psychosocial factors of pregnancy women were collected and the depression of pregnancy women was measured by self-designed questionnaire and self-rating depression scale. The Edinburgh Postnatal Depression Scale (EPDS) was applied at timepoint of one week postpartum. Single factor analysis and the unconditional multivariate logistic regression were applied for analyzing the on the related social-psychosocial factors among high-risk pregnancy women. RESULTS: The age of high-risk pregnancy women was (31.0±5.6), and the age of normal pregnancy women was (30.5±3.8) (t=0.169, P>0.05). The results showed that the depression rate in high-risk pregnancy women was 45.2% (19/42), which was 25.0% (10/40) in normal pregnancy women, the difference was significant (χ2=3.671, P=0.045). The depression rates at different time points were 30.9% (13/42), 42.9% (18/42), 23.8% (10/42), 26.2% (11/42) in high-risk pregnancy women respectively, and 25.0% (10/40), 15.0% (6/40), 20.0% (8/40), 17.5% (7/40) in the control group respectively, the difference of the depression rates among groups at one week before labor was significant (χ2=7.680, P<0.01), the difference among groups at 32-36 weeks pregnancy (χ2=0.133, P=0.80), at one week postpartum (χ2=0.174, P=0.79) and at six weeks postpartum (χ2=0.903, P=0.43) were not significant. At one week postpartum and six weeks postpartum periods, the EPDS depression rate were 12.5% (4/32), 30.4% (7/23) in case group respectively, 8.3% (3/36), 22.9% (8/35) in control group respectively, the difference were not significant (χ2=0.319, 0.416, P=0.573, 0.519). There were significantly associations between the depression mood of one week before labor and the depressive symptoms of six weeks postpartum in both groups (r=0.824, 0.677, both P values were <0.05). The risk factors for maternal depression among high-risk pregnancy women were not ready for production (OR=2.73, P<0.01) and fearing of childbirth safety (OR=2.89, P<0.01). CONCLUSION: The depression date of high-risk pregnancy was high, especially at the time point one week before labor. Risk factors of maternal depression among high-risk pregnancy were "not ready for production" and "fear of childbirth safety".

The effect of endostatin mediated by human mesenchymal stem cells on ovarian cancer cells in vitro.

INTRODUCTION: Endostatin is the most potent inhibitor of tumor angiogenesis. However, endostatin protein has a short half-time and virus-mediated endostatin gene therapy has serious toxicity, which limits the application of endostatin in clinical therapy. Mesenchymal stem cells (MSCs) are considered to be able to accumulate at the site of cancers with high specificity and may be used as a new delivery of endostatin. MATERIALS AND METHODS: The MSCs from the human bone marrow were transfected with recombinant adenovirus encoding endostatin and EGFP (MSC-EN cells). The tropism capacity of MSCs was quantitatively assayed in vitro using the Millicell system. To investigate the impact of secreted endostatin on cancer cells, SKOV3 cells were co-cultured with MSC-EN cells in Millicell for 48 h, then apoptosis and cell cycle were analyzed on a flow cytometer. RESULTS: In contrast with 293 cells and saline, SKOV3 cells significantly stimulated migration of MSCs, the number reached 919.67 +/- 19.96 (P < 0.05). The endostatin produced by MSC-EN cells made 13.08 +/- 0.21% SKOV3 cells undergo early stage apoptosis (control 3.23 +/- 0.73%, P < 0.05) and 82.05 +/- 2.65% SKOV3 cells accumulate in the G0/G1 phase (control 66.51 +/- 2.91%, P < 0.05). CONCLUSION: We found that MSCs possessed great migratory capacity in vitro and the human ovarian adenocarcinoma cell line SKOV3 could significantly induce the migration of MSCs. Our results provided evidence that MSCs could be utilized as a powerful delivery system of endostatin. The endostatin produced by MSC-EN cells could inhibit the proliferation of SKOV3 cells.

[Effects of DCC gene on cell growth and chemosensitivity of ovarian epithelial carcinoma cells].

OBJECTIVE: To study the effects of DCC gene transfection on cell-growth and chemosensitivity of ovarian epithelial carcinoma cell line HO8910. METHODS: Recombinant eukaryotic expression vector pcDNA3.1(+)-DCC containing DCC gene was introduced by lipofectamine transfection reagent into ovarian epithelial carcinoma cell line HO8910 which does not express DCC endogenously. The expression of DCC was detected by RT-PCR and immunocytochemistry. The cell proliferation and the viability rate after different concentrations of cisplatin and paclitaxel were given were assessed by methyl thiazolyl tetrazolium (MTT) assay. RESULTS: Exogenous DCC gene had been successfully transferred into HO8910 cells and obtained permanent expression. The growth speed of HO8910-DCC cells was significantly slower than other two groups. There was a significant difference between them (P < 0.01) except at the first day after being planted. There was no difference between the growth speed of HO8910 cells and that of HO8910-Neo cells (P > 0.05). The viability rate of HO8910-DCC cells was significantly lower than other two groups after (0.1 - 5.0) peak plasma concentration (PPC) of cisplatin and paclitaxel were given (P < 0.01). The viability rate of HO8910-DCC cells was lower than other two groups after 10.0 PPC concentration of cisplatin was given (P < 0.05), but there was no difference between them after 10.0 PPC concentration of paclitaxel was given (P > 0.05). The viability rate of HO8910 cells was similar to HO8910-Neo cells after different concentrations of cisplatin and paclitaxel were given (P > 0.05). CONCLUSION: The DCC gene expression not only inhibits cell growth but also enhances the chemosensitity of ovarian epithelial carcinoma cell line HO8910.