Long noncoding RNA TPTEP1 suppresses diabetic retinopathy by reducing oxidative stress and targeting the miR-489-3p/NRF2 axis.

BACKGROUND: Diabetic retinopathy (DR) is a diabetic complication with complex etiology and severe visual impairment. Dysregulated long noncoding RNAs (lncRNAs) are closely associated with DR. This article focused on the impact of lncRNA transmembrane phosphatase with tensin homology pseudogene 1 (TPTEP1) in DR. METHODS: First, sera were collected from DR patients and healthy control. Human retinal vascular endothelial cells (HRVECs) were exposed to high glucose (HG) to construct a DR model in vitro. A real-time quantitative polymerase chain reaction (RT-qPCR) was carried out to detect TPTEP1. Targeting relationships were predicted using StarBase and TargetScan, and confirmed by the Dual-Luciferase Reporter Assay. Cell Counting Kit 8 (CCK-8) and EdU staining were applied to measure cell viability and proliferation, respectively. Protein expression was determined by a western blotting assay. RESULTS: lncRNA TPTEP1 expression was significantly decreased in the serum of DR patients and HG-stimulated HRVECs. Overexpression of TPTEP1 reduced cell viability and proliferation induced by HG and oxidative stress. In addition, overexpression of miR-489-3p impaired the effects of TPTEP1. Nrf2, which was targeted by miR-489-3p, was down-regulated in HG-treatment HRVECs. Knockdown of Nrf2 enhanced the influence of miR-489-3p and antagonized the effects of TPTEP1. CONCLUSION: This study demonstrated that a TPTEP1/miR-489-3p/NRF2 axis affects the development of DR by regulating oxidative stress.

Hyperpatulones C-G, new spirocyclic polycyclic polyprenylated acylphloroglucinols from the leaves of Hypericum patulum.

Five new spirocyclic polycyclic polyprenylated acylphloroglucinols, Hyperpatulones C-G (1-5), were obtained from the leaves of Hypericum patulum. Their structures were characterized by the comprehensive analysis of their IR, NMR, CD spectra and HRESIMS data. All the new compounds were evaluated for the α-glycosidase inhibitory activities. Among them, compounds 3-5 showed α-glucosidase inhibitory activities, with IC50 values of 14.06-37.69 µM.

Hyperpatulols A-I, spirocyclic acylphloroglucinol derivatives with anti-migration activities from the flowers of Hypericum patulum.

Nine new spirocyclic acylphloroglucinol derivatives, hyperpatulols A-I (1-9), were characterized from the flowers of Hypericum patulum. Their structures were elucidated by the basic analysis of the obtained spectroscopic data, and their absolute configurations were assigned by both the electronic circular dichroism (ECD) exciton chirality method and ECD calculation. The evaluation of their anti-migration effects on U2-OS human osteosarcoma cells showed that compound 4 exhibited moderate inhibitory activity in a dose-dependent manner. Further pharmacological studies revealed that 4 could regulate the expression of the proteins Vimentin and E-cadherin.

Hypatulone A, a Homoadamantane-Type Acylphloroglucinol with an Intricately Caged Core from Hypericum patulum.

Hypatulone A (1), an acylphloroglucinol possessing an unprecedented homoadamantane architecture based on a tricyclo-[4.3.1.13,8]-undecane core and a unique 5/5/7/6/6 pentacyclic ring system, together with its biogenetic precursor hyperbeanol B (2), was isolated from Hypericum patulum. The structure of 1 was elucidated by extensive spectroscopic analysis and electronic circular dichroism calculation. Its plausible biosynthetic pathway via Wagner-Meerwein rearrangement was proposed. 1 exhibited nitric oxide inhibitory effect on LPS-induced RAW264.7 cell line (IC50 18.8 ± 1.75 µM).

Baicalin protects neonatal rat brains against hypoxic-ischemic injury by upregulating glutamate transporter 1 via the phosphoinositide 3-kinase/protein kinase B signaling pathway.

Baicalin is a flavonoid compound extracted from Scutellaria baicalensis root. Recent evidence indicates that baicalin is neuroprotective in models of ischemic stroke. Here, we investigate the neuroprotective effect of baicalin in a neonatal rat model of hypoxic-ischemic encephalopathy. Seven-day-old pups underwent left common carotid artery ligation followed by hypoxia (8% oxygen at 37°C) for 2 hours, before being injected with baicalin (120 mg/kg intraperitoneally) and examined 24 hours later. Baicalin effectively reduced cerebral infarct volume and neuronal loss, inhibited apoptosis, and upregulated the expression of p-Akt and glutamate transporter 1. Intracerebroventricular injection of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) inhibitor LY294002 30 minutes before injury blocked the effect of baicalin on p-Akt and glutamate transporter 1, and weakened the associated neuroprotective effect. Our findings provide the first evidence, to our knowledge that baicalin can protect neonatal rat brains against hypoxic-ischemic injury by upregulating glutamate transporter 1 via the PI3K/Akt signaling pathway.

Cardioprotective effect of hydrogen sulfide in ischemic reperfusion experimental rats and its influence on expression of survivin gene.

Hydrogen sulfide (H(2)S), as an endogenous gas signaling molecule with important biological function that has been found recently, may play a protection in ischemic reperfusion (I/R) myocardium. We investigated the cardioprotective effect of H(2)S in rats model of ischemic reperfusion in vivo and a probably influence on the expression of survivin, an anti-apoptosis gene. Animals were randomly divided into 3 groups and received either vehicle, sodium hydrosulfide (NaHS) or DL-propargylglycine (PAG) respectively everyday for 1 week before surgery and the treatment continued for a further 2 d after I/R till the animals were sacrificed. We investigated the plasma H(2)S concentration and blood pressure, with the electrocardiogram (ECG) together, to prove the effect of H(2)S to the heart function. We also compared the heart infarct size and the expression of an anti-apoptosis gene, survivin, among groups. As the data shown, the NaHS group had great improvement in blood pressure and electrocardiogram situation. And the remarkable shrink of the infarct size and up-regulation of survivin in NaHS group comparing with the other two groups also showed the cardio protective effect of H(2)S in our study.

Deferiprone protects the isolated atria from cardiotoxicity induced by doxorubicin.

AIM: To investigate the effects of deferiprone on doxorubicin-induced cardiotoxicity and determine its protection on cardiac contractility in vivo at tissue level. METHODS: Spontaneously-beating isolated atria from rats were pretreated with deferiprone for 10 min at 1.2 mmol/L or 0.3 mmol/L, respectively before co-incubation with doxorubicin (DOX) at 0.03 mmol/L for 60 min. Contractility (dF/dt) was assessed every 10 min during the incubation. After that, the tissues around the sinuatrial nodes were fixed for ultrastructural study; succinate dehydrogenase (SDH) and Cu, Zn superoxide dismutase (Cu, Zn-SOD) activity, as well as malondialdehyde (MDA) level of the atria were assayed. RESULTS: Treatment with DOX alone resulted in a 49.34% reduction of the contractility, mitochondria swelling, disruption of mitochondrial crista and decreased electron density of the matrices. Conversely, with the presence of deferiprone, the negative inotropic effect and lesions in the cardiac mitochondria structure induced by DOX were attenuated. Cu, Zn-SOD activity increased by 12.97%-12.11%, the MDA level decreased by 29.12%-39.82% and succinate dehydrogenase (SDH) activity was ameliorated by 25.15%-34.76%. CONCLUSION: Deferiprone can efficiently preserve cardiac contractility. Moreover, the results of this study indicate that deferiprone is able to protect mitochondrial function and structure form damage induced by DOX. This cardiac protective potential of deferiprone could be due to its defense capability against oxidative damage.