Downregulation of HS6ST2 Inhibits Cervical Cancer Cell Migration and Invasion in Vivo and in Vitro.

BACKGROUND: Emerging evidence indicates the importance of heparan sulfate 6-O-sulfotransferase 2 (HS6ST2) in a number of developmental processes. Little is known regarding its biological function in regulating cervical cancer (CC) progression. In this study, we aim to explore the role of HS6ST2 in CC progression. METHODS: The transcriptome sequencing data of CC tissues from three databases, GSE64217, GSE138080, and GSE63514, was examined for genes with significant changes. The expression profile for HS6ST2 within CC tissue was then assessed through fluorescence quantitative PCR and immunohistochemistry and compared to data from patients with clinicopathological features. A multivariate survival analysis was performed using the COX regression. The real-time quantitative PCR assessed the HS6ST2 expression profile within CC cellular cultures. The results of knocking down HS6ST2, considering the proliferative activity and invasiveness of CC cultures in vitro, were detected through cell viability assay, clonogenic assessment, tumorsphere formation analysis, 3D invasion experiment and transwell assay. The impact of HS6ST2 knockdown in CC proliferation was also evaluated in vivo using a nude mice model. RESULTS: HS6ST2 was severely upregulated within CC tissues across the three explored databases (GSE64217, GSE138080, and GSE63514). Fluorescent quantitative PCR and immunohistochemistry experiments identified HS6ST2 as highly upregulated within patients CC tissues. Survival analysis taking into account the parameters of lymph node metastasis, Federation of Gynecology and Obstetrics (FIGO) stage, depth of invasion, pathological grade, and HS6ST2 expression level demonstrated that individuals with downregulated HS6ST2 exhibited considerably extended progression-free survival (PFS) and overall survival (OS) in comparison to upregulated HS6ST2 cases. According to the findings of COX univariate analysis, the parameters lymph node metastasis, FIGO stage, depth of invasion, pathological grade, and HS6ST2 expression level, all showed a statistically significant correlation with effect upon prognosis of CC patients. The FIGO stage, depth of invasion and expression level of HS6ST2 were identified as independent risk variables influencing CC case prognosis within subsequent COX multivariate analysis. Cell function experiments proved that HS6ST2 knockdown can considerably diminish the proliferative potential, stemness and invasive traits of CC cells. Tumor formation experiments in nude mice in vivo demonstrated that knocking down HS6ST2 can significantly thwart CC cellular proliferative properties within animal models. CONCLUSIONS: The clinicopathological features and the survival time of the patients significantly correlate with the level of HS6ST2 expression in CC tissue samples.

Paeonol alleviates placental inflammation and apoptosis in preeclampsia by inhibiting the JAK2/STAT3 signaling pathway.

Preeclampsia (PE) is a multisystemic and placental inflammatory disease that causes maternal and infant health issues. As one of the active components in peony root extract, paeonol (Pae) exerts anti-apoptosis and anti-inflammatory effects. Nonetheless, the protective role of Pae in PE has not yet been characterized. A mouse model of PE was constructed through tail vein injection of 1 mg/d phosphatidylserine/dioleoyl-phosphatidycholine suspension. The levels of inflammatory cytokines in the placenta were examined via enzyme-linked immunosorbent assay (ELISA). The mRNA levels of inflammatory cytokines (TNF-α, IL-6, IFN-γ, and IL-4) and apoptosis markers (Bax, Bcl-2, and caspase-3) were tested using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blot analysis was performed to detect the protein levels of apoptosis markers and Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway-related molecules. Here, Pae repressed the inflammatory response in the placenta of PE-like mouse models, as demonstrated by the decreased concentrations and mRNA levels of TNF-α, IL-6, and IFN-γ and the increased concentrations and mRNA levels of IL-4. Apoptosis in the placentas of PE-like mouse models was attenuated by Pae, as manifested by the downregulated mRNA and protein levels of Bax and cleaved-caspase-3 and the upregulated Bcl-2. Administration of Pae inhibited the phosphorylation of JAK2 and STAT3 in the placental tissues of PE mice. The JAK2/STAT3 pathway agonist (SC-39100) reversed Pae treatment-mediated suppression of placental inflammation and apoptosis in PE mice. Overall, Pae inhibits the JAK2/STAT3 signaling pathway to attenuate placental inflammation and apoptosis in PE mice.

Birthing ball on promoting cervical ripening and its influence on the labor process and the neonatal blood gas index.

BACKGROUND: Term pregnancy-induced labor refers to the use of artificial methods to induce uterine contractions and terminate pregnancy after 37 wk. It is a common method to prevent overdue pregnancy and to deal with high-risk pregnancies. In addition, it can alleviate maternal complications and cause the fetus to leave the adverse intrauterine environment early, which is beneficial to the outcome of pregnancy. AIM: To explore the effect of a birthing ball on labor by inducing cervical ripening and its influence on labor and the neonatal blood gas index. METHODS: Twenty-two women who were scheduled to undergo labor induction and delivery in the obstetrics department of our hospital were randomly divided into two groups: the delivery ball group (childbirth ball combined with COOK balloon induction) and the conventional group (COOK balloon induction alone). The cervical Bishop score before and after intervention, duration of labor at each stage, mode of delivery, neonatal umbilical venous blood pH, oxygen partial pressure (PO2), carbon dioxide partial pressure (PCO2), and the 1-min Apgar score were recorded. RESULTS: After the intervention, the cervical Bishop score of the delivery ball group (7.84 ± 1.52) was significantly higher than that of the conventional group (7.32 ± 1.29) (P < 0.05), and the cervical Bishop scores of the two groups after intervention were significantly higher than those before intervention (P < 0.05). After the intervention, the first stage of labor (510.9 ± 98.7 min), the second stage of labor (43.0 ± 8.5 min), and the total duration of labor (560.0 ± 120.9 min) in the delivery ball group were lower than those in the routine group, with a first stage of labor of 602.1 ± 133.2 min, a second stage of labor of 48.4 ± 9.1 min, and a total duration of labor of 656.8 ± 148.5 min (P < 0.05). There was no significant difference in the time of the third stage of labor between the two groups (P > 0.05). There was no significant difference in the pH, PO2, and PCO2 values of newborns between the delivery ball group and the conventional group (P > 0.05). The 1-min Apgar score of the delivery ball group was higher than that of the conventional group (9.10 ± 0.38 points vs 8.94 ± 0.31 points, P < 0.05). The natural delivery rate of the delivery ball group was higher than that of the conventional group (91.00% vs 78.00%, P < 0.05). CONCLUSION: The use of a birthing ball combined with a COOK balloon for inducing labor has a better effect on promoting cervical ripening, shortening the time of labor, and improving the Apgar score of newborns.