Serum antiphospholipid antibody status may not be associated with the pregnancy outcomes of patients undergoing in vitro fertilization.

BACKGROUND: Antiphospholipid syndrome (APS) is an autoimmune disease that is associated with recurrent pregnancy loss. It is still controversial whether the presence of antiphospholipid antibodies (aPL) in the serum of patients with in vitro fertilization-embryo transfer (IVF-ET) has a negative effect on the outcomes. In view of the discrepancies, a meta-analysis of the published data was performed to explore the relationship of aPL and IVF-ET outcomes. METHODS: We searched for all published articles indexed in PubMed, Web of Science, and Cochrane Library, which were retrieved up to April, 2021. A total of 921 studies were yielded, of which 6 finally met the inclusion criteria. We carried out the meta-analysis by pooling results of these studies with Review Manager 5.3 software. The effect index was measured with 95% confidence intervals (CIs) of the relative risks (RRs). RESULTS: Six eligible studies were included in this meta-analysis, involving 3214 patients. Our results showed that positive aPL was not associated with decreased clinical pregnancy rate (RR 0.97; 95% CI 0.91-1.04). There was no correlation between positive aPL and increased miscarriage risk (RR 1.22; 95% CI 0.94-1.58). Only 5 of the 6 studies referred to live birth rate, but still no association was found between them (RR 0.95; 95% CI 0.81-1.11). CONCLUSIONS: The results showed that the presence of positive aPL neither decreased clinical pregnancy rate and live birth rate, nor increased miscarriage rate in women undergoing IVF, which is differed from the opinion of clinical practice. More prospective studies with high quality and larger sample size are needed to evaluate the relationship between positive aPL and outcomes of IVF-ET.

Insight of Autophagy in Spontaneous Miscarriage.

In some cases of spontaneous miscarriage (SM), the exact etiology cannot be determined. Autophagy, which is responsible for cellular survival under stress conditions, has also been implicated in many diseases. Recently, it is also surmised to be correlated with SM. However, the detailed mechanism remains elusive. In fact, there are several essential steps during pregnancy establishment and maintenance: trophoblasts invasion, placentation, decidualization, enrichment and infiltration of decidua immune cells (e.g., natural killer, macrophage and T cells). Accordingly, upstream molecules and downstream effects of autophagy are discussed in these processes, respectively. Of note, autophagy regulates the crosstalk between these cells at the maternal-fetal interface as well. Aberrant autophagy is found in villi, decidual stromal cells, peripheral blood mononuclear cells in SM patients, although the findings are inconsistent among different studies. Furthermore, potential treatments targeting autophagy are included, during which rapamycin and vitamin D are hot-spots in recent literatures. To conclude, a moderately activated autophagy is deeply involved in pregnancy, suggesting that autophagy should be a regulator and promising target for treating SM.

A positive COX-2/IL-1ß loop promotes decidualization by upregulating CD82.

A successful pregnancy requires sufficient decidualization of endometrial stromal cells (ESCs). CD82, a metastasis suppressor, is a critical regulator for trophoblast invasion but the effect in decidualization was largely unknown. Here we reported that there was a high level of CD82 in DSC by the immunohistochemistry staining and flow cytometer analysis. Stimulation with prostaglandin E2 (PGE2) elevated the expression of CD82 in ESCs. In contrast, celecoxib, a selective COX-2 inhibitor, significantly downregulated the expression of CD82 in decidual stromal cells (DSCs). Bioinformatics analysis and further research showed that recombinant human interleukin (IL)-1ß protein (rhIL-1ß) upregulated CD82 in ESCs. Of note, blocking IL-1ß signaling with anti-human IL-1ß neutralizing antibody could reverse the stimulatory effect of PGE2 on CD82 in ESCs. Silencing CD82 resulted in the decease of the decidualization markers PRL and IGFBP1 mRNA levels in DSCs. More importantly, we observed rhIL-1ß also upregulated the expression of COX-2, and the upregulation of PRL and IGFBP1 induced by rhIL-1ß could be abolished by celecoxib in ESCs or CD82 deficiency in DSCs. This study suggests that CD82 should be a novel promotor for decidualization under a positive regulation of the COX-2/PGE2/IL-1ß positive feedback loop.

[Deletion of extracellular loops of occludin affects the tight junction of TM4 cells in mice].

OBJECTIVE: To analyze the functions of the two extracellular loops of occludin in the tight junction of TM4 cells in mice. METHODS: Using genetic engineering, we separately or simultaneously deleted two extracellular loops of occludin, cloned the three occludin genes without extracellular loops into the pcDNA3.1 expression vector, and transfected them into TM4 cells. Then we determined the expression of occludin by RT-PCR and Western blot, and analyze the effects of the extracellular loops of occludin on the tight junction of the TM4 cells with the in vitro cell line model. RESULTS: The results of sequencing showed that the expression vector of pcDNA3.1 - occludin Δ OCC1, pcDNA3.1 - occludin Δ OCC2 and pcDNA3.1 - occludin Δ OCC1 + OCC2 was constructed successfully. The mRNA and protein expressions of occludin in the non-extracellular loop groups were significantly higher than in the control group. Both the extracellular loops of occludin increased the tight junction of the TM4 cells. The macromolecular permeability in the TM4 cells was significantly lower in the pcDNA3.1 - occludin Δ OCC1 than in the pcDNA3.1 - occludin Δ OCC2 group (P < 0.05), indicating a higher impact of the second than the first extracellular loop on the tight junction of the TM4 cells. CONCLUSIONS: Both of the two extracellular loops of occludin can affect the tight junction of TM4 cells, the second even more significantly than the first one.

Genetic variants of the kynurenine-3-monooxygenase and postpartum depressive symptoms after cesarean section in Chinese women.

BACKGROUND: New conceptualizations of depression have emphasized the role of the kynurenine pathway (KP) in the pathogenesis of postpartum depressive symptoms (PDS). Kynurenine 3-monooxygenase (KMO) is a rate-limiting enzyme of the KP, where it catalyzes the conversion of kynurenine (KYN) to 3-hydroxykynurenine (3-HK). Previous work indicates that KMO is closely linked to the pathophysiology of depressive disorders. The purpose of this study is to investigate whether variations in the KMO gene affect PDS development after cesarean section. METHODS: A total of 710 Chinese women receiving cesarean section were enrolled in this study. PDS was determined by an Edinburgh Postnatal Depression Scale (EPDS) score ≥13. Subsequently, 24 women with PDS and 48 matched women without PDS were randomly selected for investigation of perinatal serum concentrations of KYN, 3-HK and the 3-HK/KYN ratio. The 3-HK/KYN ratio indicates the activity of KMO. In addition, 6 single nucleotide polymorphisms of the KMO gene were examined. Following this genotyping, 36 puerperant women carrying the KMO rs1053230 AG genotype and 72 matched puerperant women carrying the KMO rs1053230 GG genotype were selected for comparisons of KYN, 3-HK and 3-HK/KYN ratio levels. RESULTS: The results show the incidence of PDS in the Chinese population to be 7.3%, with PDS characterized by increased serum 3-HK concentration and 3-HK/KYN ratio, versus matched postpartum women without PDS (P<0.05). Furthermore, polymorphisms of KMO rs1053230 are significantly associated with the incidence of PDS (P<0.05). The serum concentrations of 3-HK and the 3-HK/KYN ratio in postpartum women carrying the KMO rs1053230 AG genotype are significantly higher than those in matched postpartum women carrying the KMO rs1053230 GG genotype. CONCLUSIONS: The presented data highlight the contribution of alterations in the KP to the pathogenesis of postpartum depression. Heightened KMO activity, including as arising from KMO rs1053230 G/A genetic variations, are indicated as one possible mechanism driving the biological underpinnings of PDS.

Long-term fatigue state in postoperative patients with breast cancer.

OBJECTIVE: To investigate the prevalence of long-term fatigue, anxiety, depression and social support, and the relationships among these symptoms in postoperative patients with breast cancer. METHODS: A total of 180 postoperative patients with breast cancer meeting criterion were recruited in this cross-sectional study. The Brief Fatigue Inventory (BFI), Hospital Anxiety and Depression Scale (HADS) and The Social Support Survey-Chinese version were used to assessing the fatigue, anxiety and depression, Social support of participants. The magnitude of the relationship among the symptoms of fatigue and other variables was measured by Spearman Rho correlation. RESULTS: The prevalence of long-term fatigue was 52.7%, and 18.3% occurred moderate/severe fatigue. Two-thirds of patients had a basal social support, only 12.8% of patients had better-perceived social support. Results of HADS showed that 16.7% and 21.1% of the participants have anxiety or depression disorder. Moderate/severe fatigue was negatively correlated with social support (r=-0.158, P=0.038) and positively correlated with age (r=0.132, P=0.042), chemotherapy (r=0.297, P=0.027), anxiety (r=0.324, P=0.018) and depression (r=0.211, P=0.034). CONCLUSIONS: Long-term fatigue was highly prevalent among over half of postoperative patients with breast cancer, and moderate/severe fatigue was associated with social and psychological factors such as social support, anxiety and depression. Our results suggest that overall nursing care may be a more effective manner in improving fatigue and quality of life.

A novel colorimetric sensor of dihydrogen-phosphate based on metal complex between 8-hydroxy quinoline-5-azo-4'-nitrobenzene and cobalt.

A novel colorimetric sensor based on 8-hydroxy quinoline-5-azo-4'-nitrobenzene (1) was prepared and used for recognizing anions. 1 and its metal complex (1.Co) were found to show response to anions such as CH(3)CO(2)(-), H(2)PO(4)(-), HSO(4)(-), F(-) and dramatic color changes were observed. The selectivity and sensitivity of 1 and 1.Co for sensing anions were different, which was in the order of CH(3)CO(2)(-)>F(-)>H(2)PO(4)(-)>>HSO(4)(-) for 1 and H(2)PO(4)(-)>HSO(4)(-)>CH(3)CO(2)(-) approximately F(-) for 1.Co, respectively. In CH(3)CN, sensor 1.Co exhibited excellent specificity toward H(2)PO(4)(-), and the color variety was dependent on the concentration of H(2)PO(4)(-) which was attributed to anion structure and stability of anionic complex (1-anion), metal complex (1-Co) and inorganic complex (Co-anion).

Fluoride-selective colorimetric sensor based on thiourea binding site and anthraquinone reporter.

A structurally simple colorimetric sensor, N-4-nitrobenzene-N'-1'-anthraquinone-thiourea (1), for anions was synthesized and characterized by (1)H NMR, ESI mass and IR methods. In acetonitrile, the addition of F(-) changed 1 solution from colorless to yellow. In the presence of other anions such as CH(3)CO(2)(-), H(2)PO(4)(-), HSO(4)(-) and Cl(-), however, the absorption spectrum of 1 was slightly red shifted with no obvious color changes observed. The association constants of anionic complexes followed the order of F(-)>>CH(3)CO(2)(-)>H(2)PO(4)(-)>HSO(4)(-)>Cl(-)>Br(-), which was different from the order of anion basicity. AM1 calculation results indicated that the most stable configuration of 1 existed in the Z-E-conformation with a six-membered ring via intramolecular hydrogen bond. This made thiourea moiety of 1 in an unfavorable conformation to bond with oxygen-anionic substrates such as CH(3)CO(2)(-) and H(2)PO(4)(-), thus leading to a high selectivity and sensitivity for the detection of F(-).