Baicalin-loaded Polydopamine modified ZIF-8 NPs inhibits myocardial ischemia/reperfusion injury in rats.

Baicalin (BAN) has shown promise in alleviating myocardial ischemia/reperfusion (I/R) injury, yet its limited solubility and biocompatibility have hindered its application. Developing drug delivery systems is a promising strategy to enhance the therapeutic potential of BAN in the context of I/R injury. This study aims to prepare a BAN-loaded nanodrug system using polydopamine (PDA)-modified Zeolitic imidazolate framework-8 (ZIF-8) as a carrier, with the goal of improving BAN's mitigating effects on I/R injury. We prepared the BAN nanoparticles (NPs) system, PZB NPs, using ZIF-8 as the carrier. The system was characterized in terms of morphology, particle size, zeta potential, and X-ray diffraction (XRD). We assessed the cytotoxicity of PZB NPs in H9c2 cells, investigated its effects and mechanisms in H/R-induced H9c2 cells, and evaluated its ability to alleviate myocardial I/R injury in rats. PZB NPs exhibited good dispersion, with a BAN loading efficiency of 26.43 ± 1.55%, a hydrated particle size of 102.21 ± 1.19 nm, and a zeta potential of -24.84 ± 0.07 mV. It displayed slow and sustained drug release in an acidic environment (pH 5.5). In vitro studies revealed that PZB NPs was non-cytotoxic and significantly enhanced the recovery of H/R injury H9c2 cell viability. PZB NPs suppressed cell apoptosis, activated the Nrf2/HO-1 pathway, and cleared ROS. In vivo study demonstrated that PZB NPs significantly reduced infarct size, ameliorated fibrosis and improved heart function. The PZB NPs markedly enhances BAN's ability to alleviate I/R injury, both in vitro and in vivo, offering a promising drug delivery system for clinical applications.

Risk Factors of Ischemia Reperfusion Injury After PCI in Patients with Acute ST-Segment Elevation Myocardial Infarction and its Influence on Prognosis.

Purpose: To explore the risk factors of ischemia reperfusion injury (IRI) after percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI) and its influence on prognosis. Methods: The clinical data of 80 patients with STMEI undergoing PCI in our hospital from June 2020 to June 2021 were collected. According to whether IRI occurred after PCI, STMEI patients were divided into IRI group and non-IRI group. The basic information, clinical characteristics, examination parameters and other data of all patients were collected, and the prognosis of the two groups was observed. Risk factors were analyzed by fitting binary Logistic regression model. The survival prognosis was analyzed by Kaplan-Meier survival curve. Results: Logistic regression analysis showed that type 2 diabetes mellitus (T2DM), pre-hospital delay time (PHD) and door-to-balloon expansion time (DTB) were the influencing factors of IRI in patients with STMEI (p < 0.05). MACE occurred in 11 cases (32.35%) in the IRI group and 13 cases (28.26%) in the non-IRI group. Log-rank test showed p = 0.503, indicating no statistically significant difference. Conclusion: T2DM, PHD and DTB were the influencing factors of IRI in patients with STMEI, and IRI will not reduce the prognosis of patients.

A Review of the Role of the Antiplatelet Drug Ticagrelor in the Management of Acute Coronary Syndrome, Acute Thrombotic Disease, and Other Diseases.

P2Y12 inhibitors, including aspirin, are key components of dual-antiplatelet therapy (DAPT), which is the optimal therapeutic strategy for preventing arterial thrombosis in patients with acute coronary syndromes (ACS) who underwent stent implantation. Ticagrelor is a cyclopentyl-triazole pyrimidine antiplatelet drug that was the first reversible oral P2Y12 receptor antagonist. Compared with clopidogrel, ticagrelor exerts a faster onset and offset of function by reversible and selective inhibition of platelet aggregation in ACS patients, including those with coronary artery blood revascularization. Despite improvement in stent materials, stent thrombosis (ST) due to high on-treatment platelet reactivity (HPR) to clopidogrel continues to occur. In addition to antiplatelet aggregation, ticagrelor displays pleiotropic cardioprotective effects, including improving coronary blood flow, reducing myocardial necrosis after an ischemic event, and anti-inflammatory effects. The benefits of ticagrelor over clopidogrel were consistent in the PLATO results, with lower incidence of the primary endpoint. Also, in 2020, the findings from the phase 3 THALES trial (NCT03354429) showed that aspirin combined with 90 mg of ticagrelor significantly reduced the rates of stroke and death compared with aspirin alone in patients with AIS or TIA. Here, we review recent research on the superiority of ticagrelor over clopidogrel, discuss the pharmacological mechanism, and present future perspectives. This review aims to present the roles of ticagrelor in the management of acute coronary syndrome, acute thrombotic disease, and other diseases.

Circ_0124644 enhances ox-LDL-induced cell damages in human umbilical vein endothelial cells through upregulating FOXO4 by sponging miR-370-3p.

BACKGROUND: Circular RNA circ_0124644 has crucial regulation in the progression of coronary artery diseases, including atherosclerosis (AS). The aim of this study was to explore the regulatory mechanism of circ_0124644 in oxidized low-density lipoprotein (ox-LDL)-induced endothelial injury in human umbilical vein endothelial cells (HUVECs). METHODS: Cell viability and proliferation were assessed using cell counting kit-8 (CCK-8) assay and EdU assay. The apoptosis detection was performed by flow cytometry. Angiogenesis was evaluated through tube formation assay. The protein analysis was conducted via western blot. Inflammatory cytokines were examined by enzyme-linked immunosorbent assay (ELISA). The expression determination of circ_0124644, microRNA-370-3p (miR-370-3p) and forkhead box protein O4 (FOXO4) was performed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to analyze the interaction between targets. RESULTS: Treatment of ox-LDL resulted in the inhibition of cell viability, proliferation and angiogenesis but the promotion of apoptosis and inflammation in HUVECs. These ox-LDL-induced cell damages were alleviated after the downregulation of circ_0124644. Circ_0124644 interacted with miR-370-3p, and the regulatory role of circ_0124644 was associated with the sponge function of miR-370-3p. Additionally, miR-370-3p targeted FOXO4 and circ_0124644 increased the expression of FOXO4 through acting as a sponge of miR-370-3p. Overexpression of miR-370-3p protected from ox-LDL-induced injury via the downregulation of FOXO4. CONCLUSION: All results revealed that circ_0124644 accelerated endothelial injury in ox-LDL-treated HUVECs by mediating miR-370-3p-related FOXO4 expression.

AM1241 alleviates myocardial ischemia-reperfusion injury in rats by enhancing Pink1/Parkin-mediated autophagy.

AIMS: The purpose of this study was to reveal the therapeutic efficacy and underlying mechanism of cannabinoid type 2 receptor agonist (AM1241) on myocardial ischemia-reperfusion injury (MIRI) in rats. MAIN METHODS: We established a rat myocardial ischemia/reperfusion (I/R) model and H9c2 hypoxia/reoxygenation (H/R) model. ELISA was used to determine the concentrations of cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in plasma. EB/TTC staining was performed to observe the myocardial infarct size. Besides, the pathological changes of myocardial tissue were identified via H&E staining and Masson's trichrome staining. TUNEL assay was performed to examine myocardial apoptosis. Then, the protein expression of Pink1, Parkin and autophagy-related markers (Beclin-1, P62 and LC3) were detected by Western blot, and autophagy was evaluated by Mitotracker staining. KEY FINDINGS: The results of EB/TTC staining, H&E staining, Masson's trichrome staining and cardiac enzymes measuring showed that AM1241 treatment significantly diminished infarct size, the structural abnormalities and the activities of cardiac enzymes (cTnI, CK-MB, AST and LDH). AM1241 also significantly reduced the number of TUNEL-positive cells induced by I/R in a dose-dependent manner. Furthermore, AM1241 activated Pink1/Parkin signaling pathway and upregulated autophagy level. SIGNIFICANCE: AM1241 exerts a protective effect against MIRI in rats by inducing autophagy through the activation of Pink1/Parkin pathway.

Osthole protects against Ang II-induced endotheliocyte death by targeting NF-κB pathway and Keap-1/Nrf2 pathway.

Osthole, the main active constituents in traditional Chinese medicine fructus cnidii, has anti-inflammatory and anti-oxidant activities. Apoptosis of vascular endothelial cells is an important cause of cardiovascular disease. Inflammation and oxidative stress are two key factors in injury of endotheliocyte. In this study, we investigated the effect of osthole on Ang II-induced apoptosis of rat aortic endothelial cells (RAECs) and explored the underlying mechanisms. In the present study, the protective effects of osthole on RAECs induced by Ang II in vitro were tested. Additionally, molecular docking and molecular dynamics (MD) simulations were utilized to investigate the potential binding mode of osthole to NF-κB and Keap1. Our results showed osthole remarkably attenuates Ang II-induced apoptosis of RAECs via alleviating inflammation and oxidative stress. Molecular docking and MD simulations revealed the potential interaction of osthole bind to the P65 subunit of NF-κB and the Keap1 protein, an adaptor for the degradation of Nrf2. We further found that osthole decreased Ang II-induced inflammation and oxidative stress through respectively modulating NF-κB and Nrf2 pathways in RAECs. These studies provide evidence that osthole may represent a potential therapeutic agent for the treatment of vascular injury.

Clinical and molecular features of a Han Chinese family with maternally transmitted hypertension.

Mutations in mitochondrial DNA (mtDNA) were found to be associated with hypertension. We reported here clinical, genetic and molecular characterization of a Han Chinese family with maternally inherited hypertension. Most strikingly, this family exhibited a high penetrance of hypertension. Sequence analysis of the entire mitochondrial genome showed the presence of the well-known T4363C mutation in tRNAGln, as well as the ND1 T3394C mutation, and a set of polymorphisms belonging to human mitochondrial haplogroup M7b. Of these, the T4363C mutation was localized at the highly conserved nucleotide in the anticodon stem of tRNAGln (position 38), may result the failure in tRNA metabolism. Moreover, the homoplasmic ND1 T3394C mutation, which had been reported to be associated with Leber's hereditary optic neuropathy (LHON), was regarded as a pathogenic mutation associated with mitochondrial diseases. Thus, the combination of ND1 T3394C and tRNAGln T4363C mutations may contribute to the high penetrance and expressivity of hypertension in this Chinese family.

[Exploration on serum metabolic biomarkers of hepatitis B virus infected patients based on gas chromatography-mass spectrometry].

Abstract: The difference of serum metabolome between hepatitis B virus (HBV) infected patients and healthy controls was explored for the potential metabolite biomarkers of HBV disease using serum metabolomics approach. Totally 30 HBV infected patients and 35 healthy controls were enrolled. Gas chromatography-time-of-flight mass spectrometry (GC-TOFMS), pattern recognition by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were applied in each group. Several metabolites which were different between the two groups based on variable importance in projection (VIP) value, non-parametric test and screening in databases were identified. Ten variables that were significantly different were considered as the potential biomarkers, among which five variables (citric acid, aconitic acid, glutamine, N,N-dimethylglycine and malonic acid) showed good correlation with HBV patients. The area under the receiver operating characteristic curve was 0.975, with good specificity and sensitivity. A panel of metabolite markers composed of citric acid, aconitic acid, glutamine, N,N-dimethylglycine and malonic acid from GC-TOFMS were selected to discriminate HBV subjects from their healthy counterparts. These biochemical changes provide a novel molecular diagnostic approach which could be helpful to further understand the pathogenesis and identify the therapeutic target of HBV disease.