Defective Uterine Spiral Artery Remodeling and Placental Senescence in a Pregnant Rat Model of Polycystic Ovary Syndrome.

Pregnancy-related problems have been linked to impairments in maternal uterine spiral artery (SpA) remodeling. The mechanisms underlying this association are still unclear. It is also unclear whether hyperandrogenism and insulin resistance, the two common manifestations of polycystic ovary syndrome, affect uterine SpA remodeling. We verified previous work in which exposure to 5-dihydrotestosterone (DHT) and insulin (INS) in rats during pregnancy resulted in hyperandrogenism, insulin intolerance, and higher fetal mortality. Exposure to DHT and INS dysregulated the expression of angiogenesis-related genes in the uterus and placenta and also decreased expression of endothelial nitric oxide synthase and matrix metallopeptidases 2 and 9, increased fibrotic collagen deposits in the uterus, and reduced expression of marker genes for SpA-associated trophoblast giant cells. These changes were related to a greater proportion of unremodeled uterine SpAs and a smaller proportion of highly remodeled arteries in DHT + INS-exposed rats. Placentas from DHT + INS-exposed rats exhibited decreased basal and labyrinth zone regions, reduced maternal blood spaces, diminished labyrinth vascularity, and an imbalance in the abundance of vascular and smooth muscle proteins. Furthermore, placentas from DHT + INS-exposed rats showed expression of placental insufficiency markers and a significant increase in cell senescence-associated protein levels. Altogether, this work demonstrates that increased pregnancy complications in polycystic ovary syndrome may be mediated by problems with uterine SpA remodeling, placental functionality, and placental senescence.

A Water-Soluble Copper-Polypyridine Complex as a Homogeneous Catalyst for both Photo-Induced and Electrocatalytic O2 Evolution.

The water-soluble polypyridine copper complex [Cu(F3TPA)(ClO4)2] [1; F3TPA=tris(2-fluoro-6-pyridylmethyl)amine] catalyzes water oxidation in a pH 8.5 borate buffer at a relatively low overpotential of 610 mV. Assisted by photosensitizer and an electron acceptor, 1 also exhibits activity as a homogeneous catalyst for photo-induced O2 evolution with a maximum turnover frequency (TOF) of (1.58 ± 0.03) × 10(-1) s(-1) and a maximum turnover number (TON) of 11.61 ± 0.23. In comparison, the reference [Cu(TPA)(ClO4)2] [TPA=tris(2-pyridylmethyl)amine] displayed almost no activity under either set of conditions, implying the crucial role of the ligand in determining the behavior of the catalyst. Experimental evidence indicate the molecular catalytic nature of 1, leading to a potentially practical strategy to apply the copper complex in a photoelectrochemical device for water oxidation.

Regulatory mechanisms of HMGB1 and its receptors in polycystic ovary syndrome-driven gravid uterine inflammation.

High-mobility group box 1 (HMGB1) is critical for inflammatory homeostasis and successful pregnancy, and there is a strong association among elevated levels of HMGB1, polycystic ovary syndrome (PCOS), chronic inflammation and pregnancy loss. However, the mechanisms responsible for PCOS-driven regulation of uterine HMGB1 and its candidate receptors [toll-like receptor (TLR) 2 and 4] and inflammatory responses during pregnancy remain unclear. In this study, we found a gestational stage-dependent decrease in uterine HMGB1 and TLR4 protein abundance in rats during normal pregnancy. We demonstrated that increased expression of HMGB1, TLR2 and TLR4 proteins was associated with activation of inflammation-related signalling pathways in the gravid uterus exposed to 5α-dihydrotestosterone and insulin, mimicking the clinical features (hyperandrogenism and insulin resistance) of PCOS and this elevation was completely inhibited by treatment with the androgen receptor (AR) antagonist flutamide. Interestingly, acute exposure to lipopolysaccharide suppressed HMGB1, TLR4 and inflammation-related protein abundance but did not affect androgen levels or AR expression in the gravid uterus with viable fetuses. Furthermore, immunohistochemical analysis revealed that, in addition to being localized predominately in the nuclear compartment, HMGB1 immunoreactivity was also detected in the cytoplasm in the PCOS-like rat uterus, PCOS endometrium and pregnant rat uterus with haemorrhagic and resorbed fetuses, possibly via activation of nuclear factor κB signalling. These results suggest that both AR-dependent and AR-independent mechanisms contribute to the modulation of HMGB1/TLR2/TLR4-mediated uterine inflammation. We propose that the elevation of HMGB1 and its receptors and disruption of the pro-/anti-inflammatory balance in the gravid uterus may participate in the pathophysiology of PCOS-associated pregnancy loss.

A Signature of Three Apoptosis-Related Genes Predicts Overall Survival in Breast Cancer.

Background: The commonest malignancy in women is known as breast cancer (BC). Numerous studies demonstrated that apoptosis appears to be critical to the management and clinical outcome of BC patients. The purpose of this study is to explore the potential connection between apoptosis and BC and establish the apoptosis-associated gene signature in BC. Methods: The data of BC patient transcripts and related clinical information comes from the Cancer Genome Atlas Database (TCGA), and the genes related to apoptosis come from the Molecular Characterization Database (MSigDB). We identified the abnormally expressed apoptosis-related genes in BC samples. The optimal apoptosis-related genes screened by Cox regression analysis were designed to construct a prognostic model for predicting BC patients. Using the Nom Chart to Predict 1-Year, 3-Year, and 5-Year overall survival for BC patients. The gene signature-related functional pathways were explored by gene set enrichment analysis (GSEA). Results: Three genes [alpha subunit of the interleukin 3 receptor (IL3RA), apoptosis-inducing factor mitochondrial-associated 1 (AIFM1), and phosphatidylinositol-3 kinase catalytic alpha (PIK3CA)] correlated with apoptosis were shown to be strongly linked to the overall survival of BC. Survival analysis shows that the risk score is directly proportional to the poor prognosis of BC patients. Risk assessment based on three genetic characteristics (age, pathological stage N, and pathological stage M) can independently predict the prognosis of patients with BC. The Nom chart is most suitable for assessing the long-term survival rate of BC patients. The results of GSEA demonstrated that numerous cell cycle-related pathways were abundant in the high-risk group. Conclusion: We constructed an apoptosis-associated gene signature in BC, which had a potential clinical application prospect for BC patients.

A New Route to Liposil Formation by an Interfacial Sol-Gel Process Confined by Lipid Bilayer.

We report a new and simple approach to prepare a class of silica-reinforced liposomes with hybrid core-shell nanostructures. The amphiphilic natural structure of lipids was exploited to sequester hydrophobic molecules, namely precursor TEOS and pyrene, in the hydrophobic midplane of liposomal bilayer assemblies in the aqueous phase. Subsequent interfacial hydrolysis of TEOS at the bilayer/water interface and ensuing condensation within the hydrophobic interstices of the lipid bilayer drives silica formation in situ, producing a novel class of silica-lipid hybrid liposils. Structural characterization by scanning- and transmission electron microscopy confirm that the liposils so generated preserve closed topologies and size-monodipersity of the parent lecithin liposomes, and DSC-TGA and XRD measurements provide evidence for the silica coating. Monitoring fluorescence measurements using embedded pyrene yield detailed information on microenvironment changes, which occur during sol-gel process and shed light on the structural evolution during silica formation. We envisage that liposils formed by this simple, new approach, exploiting the hydrophobic core of the lipid bilayer to spatially localize silica-forming precursors enables preparation of stable liposils exhibiting capacity for cargo encapsulation, bicompatibility, and fluorescence monitoring, more generally opening a window for construction of stable, functional hybrid materials.