Coronary artery disease (CAD) is a major cardiovascular disease responsible for high morbidity and mortality worldwide. The major pathophysiological basis of CAD is atherosclerosis in association with varieties of immunometabolic disorders that can suppress oxytocin (OT) receptor (OTR) signaling in the cardiovascular system (CVS). By contrast, OT not only maintains cardiovascular integrity but also has the potential to suppress and even reverse atherosclerotic alterations and CAD. These protective effects of OT are associated with its protection of the heart and blood vessels from immunometabolic injuries and the resultant inflammation and apoptosis through both peripheral and central approaches. As a result, OT can decelerate the progression of atherosclerosis and facilitate the recovery of CVS from these injuries. At the cellular level, the protective effect of OT on CVS involves a broad array of OTR signaling events. These signals mainly belong to the reperfusion injury salvage kinase pathway that is composed of phosphatidylinositol 3-kinase-Akt-endothelial nitric oxide synthase cascades and extracellular signal-regulated protein kinase 1/2. Additionally, AMP-activated protein kinase, Ca 2+ /calmodulin-dependent protein kinase signaling and many others are also implicated in OTR signaling in the CVS protection. These signaling events interact coordinately at many levels to suppress the production of inflammatory cytokines and the activation of apoptotic pathways. A particular target of these signaling events is endoplasmic reticulum (ER) stress and mitochondrial oxidative stress that interact through mitochondria-associated ER membrane. In contrast to these protective effects and machineries, rare but serious cardiovascular disturbances were also reported in labor induction and animal studies including hypotension, reflexive tachycardia, coronary spasm or thrombosis and allergy. Here, we review our current understanding of the protective effect of OT against varieties of atherosclerotic etiologies as well as the approaches and underlying mechanisms of these effects. Moreover, potential cardiovascular disturbances following OT application are also discussed to avoid unwanted effects in clinical trials of OT usages.

BackgroundMenopause is the most important sign of aging in women, and the ovary is the organ most sensitive to aging. Quercetin is a potential antioxidant and free radical scavenger that is widely found in fruits, vegetables, and leaves. However, the effect of quercetin on ovarian aging has not been elucidated, and the mechanism underlying its antioxidative effect remains unclear. The purpose of the current study was to investigate whether quercetin protects ovarian function by decreasing oxidative stress.MethodsIn an in vivo experiment, female menopausal rats (12 months old) were intragastrically administered quercetin at three doses (12.5 mg/kg, 25 mg/kg, and 50 mg/kg) for 90 days, and the estrous cycles were determined by vaginal smearing. In an in vitro experiment, rat primary ovarian granulosa cells were cultured and treated with H2O2 (400 μM) alone or H2O2 plus quercetin at 5 μM, 20 μM, or 50 μM. The levels of the hormones estradiol (E2), progesterone (P), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were detected by radioimmunoassay. The serum levels of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-PX) and glutathione S-transferase (GST) were examined. The expression levels of the oxidative stress-related genes SOD-1, catalase (CAT) and glutathione synthetase (GSS) in the ovaries and ovarian granulosa cells were detected by Western blot.ResultsThe in vivo results demonstrated that quercetin had no effects on ovarian morphology, hormone secretion, or the estrous cycle in menopausal rats. Although no significant changes were detected in the serum levels of T-AOC, SOD, GSH, GSH-PX, and GST between the quercetin and control groups, the mRNA and protein expression levels of the oxidative stress-related genes SOD-1, CAT and GSS in menopausal rat ovaries were increased by low-dose quercetin. Moreover, the in vitro results demonstrated that quercetin significantly rescued the decrease in cell viability by H2О2-induced oxidative stress and enhanced the H2O2-induced decrease in expression of oxidative stress-related proteins.ConclusionsTogether, the results of this study indicated that quercetin increased the antioxidant capacity of the ovary by upregulating the expression of some oxidative stress-related genes both in vivo and in vitro.

Background: Long noncoding RNAs have been proven to play an important role in the progression of Alzheimer’s disease (AD). However, the function of small nucleolar RNA host gene 1 (SNHG1) in AD progression remains to be studied. Objective: To explore the role of SNHG1 in AD progression and clarify its potential mechanism. Methods: Amyloid β-protein (Aβ) was used to construct an AD cell model in vitro. The expression levels of SNHG1 and miR-361-3p were determined by quantitative real-time polymerase chain reaction. Cell viability and apoptosis were measured by cell counting kit 8 assay and flow cytometry. The levels of apoptosis-related proteins and zinc finger gene 217 (ZNF217) protein were evaluated by western blot analysis. Additionally, the contents of inflammatory cytokines and oxidative stress markers were tested by enzyme-linked immunosorbent assay. Furthermore, dual-luciferase reporter and RNA immunoprecipitation assays were used to verify the interaction between miR-361-3p and SNHG1 or ZNF217. Results: Aβ could induce cell injury, while resveratrol could reverse this effect. SNHG1 expression was positively regulated by Aβ and negatively regulated by resveratrol. SNHG1 knockdown could reverse the promotion effect of Aβ on cell injury. Moreover, SNHG1 sponged miR-361-3p, and miR-361-3p targeted ZNF217. Additionally, miR-361-3p overexpression reversed the promotion effect of SNHG1 overexpression on cell injury, and ZNF217 silencing also reversed the promotion effect of miR-361-3p inhibitor on cell injury. Conclusion: SNHG1 promoted cell injury by regulating the miR-361-3p/ZNF217 axis, which might provide a theoretical basis for molecular therapy of AD.

Glucose transport across the placenta is mediated by glucose transporters (GLUT), which is critical for normal development and survival of the fetus. Regulatory mechanisms of GLUT in placenta have not been elucidated. Placental CRH has been implicated to play a key role in the control of fetal growth and development. We hypothesized that CRH, produced locally in placenta, could act to modulate GLUT in placenta. To investigate this, we obtained human placentas from uncomplicated term pregnancies and isolated and cultured trophoblast cells. GLUT1 and GLUT3 expressions in placenta were determined, and effects of CRH on GLUT1 and GLUT3 were examined. GLUT1 and GLUT3 were identified in placental villous syncytiotrophoblasts and the endothelium of vessels. Treatment of cultured placental trophoblasts with CRH resulted in an increase in GLUT1 expression while a decrease in GLUT3 expression in a dose-dependent manner. Cells treated with either CRH antibody or nonselective CRH receptor (CRH-R) antagonist astressin showed a decrease in GLUT1 and an increase in GLUT3 expression. CRH-R1 antagonist antalarmin decreased GLUT1 expression while increased GLUT3 expression. CRH-R2 antagonist astressin2b increased the expression of both GLUT1 and GLUT3. Knockdown of CRH-R1 decreased GLUT1 expression while increased GLUT3 expression. CRH-R2 knockdown caused an increase in both GLUT1 and GLUT3 expression. Our data suggest that, in placenta, CRH produced locally regulates GLUT1 and GLUT3 expression, CRHR1 and CRHR2-mediated differential regulation of GLUT1 and GLUT3 expression. Placental CRH may regulate the growth of fetus and placenta by modulating the expression of GLUT in placenta during pregnancy.