Association between disease activity of rheumatoid arthritis and maternal and fetal outcomes in pregnant women: a systematic review and meta-analysis.

BACKGROUND: A meta-analysis has compared the pregnancy outcomes between women with and without RA, while the effect of disease severity on pregnancy outcomes within women with RA has not been explored. Therefore, we performed a systematic review and meta-analysis to assess the association between disease activity of RA and pregnancy outcomes. METHODS: Four English databases (Pubmed, Embase, Cochrane Library, and Web of Science) and three Chinese databases (China National Knowledge Infrastructure [CNKI], VIP, and Wan Fang) was searched for eligible studies up to August 13, 2023. Cochran's Q test and the I2 statistic were used to assess the heterogeneity of the included studies. The odds ratio (OR) (for counting data) and weighted mean difference (WMD) (for measurement data) were calculated with 95% confidence intervals (95%CIs) using random-effect model (I2 ≥ 50%) or fixed-effect model (I2 < 50%). Subgroup analysis based on study design and regions was used to explore the sources of heterogeneity. Sensitivity analysis was performed for all outcomes and the publication bias was assessed using Begg's test. RESULTS: A total of 41 eligible articles were finally included. RA women had higher odds to suffer from preeclampsia, gestational diabetes, spontaneous abortion, and cesarean delivery (all P < 0.05). The infants born from RA mother showed the higher risk of stillbirth, SGA, LBW, congenital abnormalities, diabetes type 1, and asthma (all P < 0.05). The high disease activity of RA was significantly associated with the higher risk of cesarean delivery (OR: 2.29, 95%CI: 1.02-5.15) and premature delivery (OR: 5.61, 95%CI: 2.20-14.30). CONCLUSIONS: High disease activity of RA was associated with the high risk of adverse pregnancy outcomes, suggesting that it was important to control disease for RA women with high disease activity who prepared for pregnancy.

Microglia activation induces oxidative injury and decreases SIRT3 expression in dopaminergic neuronal cells.

Microglia activation-mediated neuroinflammation plays an important role in the progression of Parkinson's disease (PD). However, effects of microglia activation on dopaminergic neuronal cell (DAC) fate are still poorly understood. The objective of this study was to explore the neurotoxic effects of microglia activation-mediated oxidative injury in DACs and its possible mechanisms. In the present study, microglia-DACs co-culture systems (murine BV-2 and MN9D cells, or primary microglia and mesencephalic neurons) were used to display the crosstalk between both cell types. The cytotoxicity of lipopolysaccharide-induced microglia activation led to the accumulation of intracellular reactive oxygen species, increased cell apoptosis rate, reduced number of DACs, concomitant to cell cycle arrest at G1 phase. Molecular mechanisms of apoptosis caused by microglia activation-induced oxidative injury included the increased opening of mitochondrial permeability transition pore and enhanced membrane potential depolarization in MN9D cells, down-regulation of Bcl-2 and up-regulation of Bax, caspase-3 expression in DACs. In addition, microglia activation made a significant reduction of SIRT3 and superoxide dismutase 2 gene expression in DACs. Taken together, these data imply that microglia activation promotes cell apoptosis through mitochondrial pathway and decreases SIRT3 expression in DACs, which may provide some support for PD progression promoted by neuroinflammation.

Recurrence of diet-treated gestational diabetes in primiparous women in northern Zhejiang, China: Epidemiology, risk factors and implications.

AIM: This study sought to determine the rate of recurrence of gestational diabetes mellitus (GDM) recurrence during the second pregnancies of women who were diagnosed with GDM during their first pregnancies, to identify risk factors associated with the probability of such recurrence and to evaluate the influence of GDM recurrence on pregnancy outcomes in north Zhejiang, China, after the recent adjustment to the nation's childbirth policy. METHODS: A retrospective longitudinal study was performed in north Zhejiang, China (at Jiaxing Maternal and Child Health Hospital). A total of 128 women who delivered two sequential live singleton infants and were diagnosed with diet-treated GDM during their first pregnancies were included. RESULTS: According to the 2013 World Health Organization diagnostic criteria for diabetes during pregnancy, the prevalence of gestational diabetes was 11.02% in northern Zhejiang. The recurrence rate of GDM in northern Zhejiang was 43.75% (56/128). The age at second pregnancy, weight gain during pregnancy, interpregnancy interval and macrosomia during the index pregnancy were risk factors for GDM recurrence. Among those women with recurrent GDM, GDM developed earlier and caesarean section was more frequently required during the second pregnancy; in addition, the second pregnancy was associated with more premature and low birthweight infants but less macrosomia. CONCLUSION: The recurrence rate of GDM is high in northern Zhejiang. Glucose monitoring and management are needed during subsequent pregnancies for patients who previously presented with GDM to improve maternal and fetal outcomes.

Therapeutic effect of E-Lip-siRNA-sFlt1 on pre-eclampsia: targeted gene silencing and improved pregnancy outcomes.

Aim: To evaluate a liposome complex conjugated with anti-epidermal growth factor receptor (EGFR) antibodies for the treatment of pre-eclampsia (PE).Methods: In in vitro experiments, the transfection rate, silencing effect and cytotoxicity were determined. In the in vivo PE model, the siRNA distribution, mean arterial pressure, 24-h urine protein concentration, serum sFlt1 concentration, number of viable fetuses and placental weight were measured.Results: The nanomedicine effectively reduced the expression of sFIt1 and had a strong ability to target placental tissues. It could significantly reduce the symptoms of pre-eclampsia and improve pregnancy outcomes in PE model rats.Conclusion: The constructed nanomedicine can improve pregnancy outcomes in a rat model of pre-eclampsia and provides a new strategy for the treatment of pre-eclampsia.

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EGFR aptamer-conjugated liposome-polycation-DNA complex for targeted delivery of SATB1 small interfering RNA to choriocarcinoma cells.

Choriocarcinoma is a highly aggressive and vascular cancer. The main treatment for choriocarcinoma is the chemotherapy associated with severe side effects. Therefore, the development of novel strategies to eliminate choriocarcinoma is crucial for increasing the health of women. SATB1 (special AT-rich sequence binding protein 1) participates in tissue-specific gene expression and higher-order chromatin organization, and could promote cancer progression and invasion. For the first time, we hereby demonstrated that the expression of SATB1 was increased by 19 folds in choriocarcinoma cells compared with the normal chorionic cell line, and inhibition of SATB1 expression could markedly inhibit the proliferation of choriocarcinoma cells. Then we developed the gene drug delivery system EGFR-LPDS (epidermal growth factor receptor aptamer-conjugated liposome-polycation-DNA complex loaded with SATB1 siRNA) to increase the delivery and therapeutic effect of SATB1 siRNA against choriocarcinoma cells. The results showed that EGFR-LPDS could specifically target choriocarcinoma cells, resulting in significant inhibition of SATB1 expression, growth inhibitory effect and apoptosis in EGFR over-expressing choriocarcinoma cells in vitro. Notably, EGFR-LPDS could inhibit the expression of SATB1 in choriocarcinoma xenograft in mice, and exhibited the best therapeutic efficacy against mice bearing choriocarcinoma xenograft compared with other controls. Notably, EGFR-LPDS achieved a striking tumor weight inhibitory rate of 81.4%. This is the first report of the therapeutic efficacy of SATB1 siRNA towards choriocarcinoma, and the increased SATB1 siRNA delivery by nanoparticles to choriocarcinoma cells using EGFR aptamers. Thus, EGFR-LPDS represents an up-and coming approach for choriocarcinoma therapy. Considering that there are still limited treatment strategies for choriocarcinoma therapy, patients with choriocarcinoma may be beneficial from this gene therapy.