• Molecular mechanisms
• Myocardial I/R injury
• ROS
• Sirtuins
• Therapeutic modalities

• 2100220171 Liaoning University of Traditional Chinese Medicine Provincial Key Laboratory Post-Subsidy Program

• Prussian blue nanozyme
• anti-inflammation
• myocardial ischemia-reperfusion injury
• polydextrose-sorbitol carboxymethyl ether
• reactive oxygen species

• Myocardial Reperfusion Injury/drug therapy
• Myocardial Reperfusion Injury/pathology
• Myocardial Reperfusion Injury/metabolism
• Ferrocyanides/chemistry
• Ferrocyanides/pharmacology
• Animals
• Mice
• Superoxide Dismutase/metabolism
• Superoxide Dismutase/chemistry
• Reactive Oxygen Species/metabolism
• Male
• RAW 264.7 Cells
• Humans

• Biomaterial assemblies
• Endometrial injury
• Extracellular vesicles
• MicroRNA
• Regenerative repair
• Umbilical cord mesenchymal stem cells

• Cell survival
• H9c2
• Mitochondrial membrane potential
• Nanotechnology
• Oxidative stress

• Animals
• Rats
• Myocytes, Cardiac/metabolism
• Terbium/metabolism
• Terbium/pharmacology
• Terbium/therapeutic use
• Phosphatidylinositol 3-Kinases/metabolism
• Cell Line
• Hypoxia/metabolism
• Myocardial Reperfusion Injury/drug therapy
• Myocardial Reperfusion Injury/metabolism
• Nanotubes

• Molecular mechanisms
• Myocardial ischemia-reperfusion injury
• Prevention

As an adjuvant drug, alprostadil lipid microsphere injection (Lipo-PGE₁) is one of the best-selling drugs in China in recent years. However, the off-label use of Lipo-PGE₁ is very common. This study aimed to investigate the use of Lipo-PGE₁ and evaluate the clinical effects and economic benefits after administrative intervention on inappropriate use of Lipo-PGE₁ in neurosurgical patients in a Chinese tertiary hospital. Administrative interventions were implemented from January to December 2018 by reducing the procurement volume of Lipo-PGE₁, judging the rationality of medical records, and establishing reward and punishment mechanisms. Administrative interventions significantly decreased prescription rate (49.98% vs 22.49%), utilization (22,311 DDDs vs 8334 DDDs), drug use density (43.52 DDDs/TID vs 15.84 DDDs/TID), total expenditure (3.58 million RMB vs 1.30 million RMB), and average expenditure (2025.04 RMB vs 1466.49 RMB) of Lipo-PGE₁. To our delight, these intervention effects were maintained or even better in the 1-year post-intervention period. Moreover, in the intervention and post-intervention phases, the Lipo-PGE₁ use for no indications as well as inappropriate drug dose, frequency, menstruum type, combination, and contraindication were markedly reduced. Besides, the mean costs (P < 0.001), and mean duration (P < 0.001) of Lipo-PGE₁ were also obviously decreased. The administrative intervention obviously reduced the off-label use of Lipo-PGE₁. However, there still remains a number of inappropriate uses of Lipo-PGE₁. To further improve the rational use of Lipo-PGE₁, combination of administrative intervention and real-time clinical pharmacists intervention should be implemented.

• Apoptosis
• Cardiac function
• Long non-coding RNA LINC00461
• Myeloid differentiation primary response gene 88
• Myocardial ischemia–reperfusion
• Oxidative stress
• microRNA-185-3p

• B-cell lymphoma 2
• Cerebral ischemic injury
• Histone deacetylases 4
• Sevoflurane
• microRNA-203-3p

Interventional coronary reperfusion strategies are widely adopted to treat acute myocardial infarction, but morbidity and mortality of acute myocardial infarction are still high. Reperfusion injuries are inevitable due to the generation of reactive oxygen species (ROS) and apoptosis of cardiac muscle cells. However, many antioxidant and anti-inflammatory drugs are largely limited by pharmacokinetics and route of administration, such as short half-life, low stability, low bioavailability, and side effects for treatment myocardial ischemia reperfusion injury. Therefore, it is necessary to develop effective drugs and technologies to address this issue. Fortunately, nanotherapies have demonstrated great opportunities for treating myocardial ischemia reperfusion injury. Compared with traditional drugs, nanodrugs can effectively increase the therapeutic effect and reduces side effects by improving pharmacokinetic and pharmacodynamic properties due to nanodrugs’ size, shape, and material characteristics. In this review, the biology of ROS and molecular mechanisms of myocardial ischemia reperfusion injury are discussed. Furthermore, we summarized the applications of ROS-based nanoparticles, highlighting the latest achievements of nanotechnology researches for the treatment of myocardial ischemia reperfusion injury.

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Cardiovascular diseases are the leading cause of death worldwide. Researches of the myocardial infarction pathology and development of new treatments have very important scientific significance in the biomedical field.

• Antioxidant therapy
• Myocardial ischemia reperfusion injury
• Nano-enzyme
• Nanocarrier
• Reactive oxygen species

• biomarkers
• cardiac dysfunction
• cardiac injury
• inflammatory mediators
• severe acute pancreatitis
• treatment

Coronary microembolization (CME) results in progressive contractile dysfunction associated with cardiomyocyte apoptosis. Alprostadil injection improves microcirculation, which is effective in treating various cardiovascular disorders. However, the therapeutic effects of alprostadil in CME-induced myocardia injury remain unknown. Therefore, we evaluated the effects of alprostadil injection on cardiac protection in a rat model of CME and explored the underlying mechanisms.

A rat model of CME was established by injecting polyethylene microspheres into the left ventricle. After injection of microspheres, rats in the alprostadil group received alprostadil via tail vein within 2 minutes. Cardiac function, histological alterations in myocardium, serum c-troponin I (cTnI) levels, myocardium adenosine triphosphate (ATP) concentrations, the activity of superoxide dismutase (SOD) and malondialdehyde (MDA) content in myocardium, and myocardial apoptosis-related proteins were detected 12 hours after CME modeling.

Compared with the Sham group, ATP concentrations, SOD activity in the myocardium, and cardiac function were significantly decreased in a rat model of CME. In addition, serum cTnI levels, MDA content, expression levels of pro-apoptotic proteins, and the number of TUNEL-positive nuclei were remarkably higher in CME group than those in the Sham group. However, alprostadil treatment notably reduced serum cTnI levels and expression levels of pro-apoptotic proteins, while noticeably improved cardiac function, and accelerated SOD activity in the myocardium following CME. Additionally, it was unveiled that the protective effects of alprostadil injection inhibit CME-induced myocardial apoptosis in the myocardium potentially through regulation of the GSK-3β/Nrf2/HO-1 signaling pathway.

Alprostadil injection seems to significantly suppress oxidative stress, alleviate myocardial apoptosis in the myocardium, and improve cardiac systolic and diastolic functions following CME by regulating the GSK-3β/Nrf2/HO-1 signaling pathway.

• GSK-3β/Nrf2/HO-1 signaling pathway
• alprostadil injection
• apoptosis
• coronary microembolization

• Asymmetric dimethylarginine (ADMA)
• Cadmium
• Endothelial dysfunction
• Endothelial nitric oxide synthase (eNOS)

• Animals
• Arginine/analogs & derivatives
• Cadmium
• Endothelium, Vascular
• Male
• Nitric Oxide
• Rats
• Rats, Sprague-Dawley

• Qatar University

• COX-1
• COX-2
• Cardiac arrest
• Cyclooxygenase inhibition
• Heart rate variability
• Ischemia reperfusion
• NSAID
• Nonsteroidal anti-inflammatory
• Prostaglandins

• Animals
• Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
• Autonomic Nervous System/drug effects
• Cyclooxygenase 1/metabolism
• Cyclooxygenase 2/metabolism
• Cyclooxygenase Inhibitors/pharmacology
• Disease Models, Animal
• Heart Arrest/drug therapy
• Heart Arrest/prevention & control
• Heart Rate/drug effects
• Humans
• Male
• Mice
• Registries
• Reperfusion Injury/physiopathology
• Swine
• Treatment Outcome
• Troponin I/metabolism
• Ventricular Fibrillation/drug therapy
• Ventricular Fibrillation/mortality
• Ventricular Fibrillation/physiopathology

To reveal the function of miR-134 in myocardial ischemia.

Real-time PCR and western blotting were performed to measure the expression of miR-134, nitric oxide synthase 3 (NOS3) and apoptotic-associated proteins. Lactic dehydrogenase (LDH) assay, cell counting kit-8 (CCK-8), Hoechst 33342/PI double staining and flow cytometry assay were implemented in H9c2 cells, respectively. MiR-134 mimic/inhibitor was used to regulate miR-134 expression. Bioinformatic analysis and luciferase reporter assay were utilized to identify the interrelation between miR-134 and NOS3. Rescue experiments exhibited the role of NOS3. The involvement of PI3K/AKT was assessed by western blot analysis.

MiR-134 was high regulated in the myocardial ischemia model, and miR-134 mimic/inhibitor transfection accelerated/impaired the speed of cell apoptosis and attenuated/exerted the cell proliferative prosperity induced by H/R regulating active status of PI3K/AKT signaling. LDH activity was also changed due to the different treatments. Moreover, miR-134 could target NOS3 directly and simultaneously attenuated the expression of NOS3. Co-transfection miR-134 inhibitor and pcDNA3.1-NOS3 highlighted the inhibitory effects of miR-134 on myocardial H/R injury.

This present work puts insights into the crucial effects of the miR-134/NOS3 axis in myocardial H/R injury, delivering a potential therapeutic technology in future.

Alprostadil can inhibit inflammation and reduce inflammation-related injury in many inflammatory diseases. However, the anti-inflammatory effect of alprostadil in decreasing acute pancreatitis (AP) injury remains unknow. This study aimed to investigate the possible protective effects and mechanism of alprostadil against AP in rats.

Forty healthy Sprague-Dawley rats were randomly divided into a control group, an AP group, an AP-alprostadil group, an AP-AG490 group, and an AP-(alprostadil+AG490) group. An animal model of acute pancreatitis was established. The pathological changes of the pancreases in each group were observed. We assessed levels of malondialdehyde (MDA), superoxide dismutase (SOD), and myeloperoxidase (MPO), as well as serum IL-1β, IL-6, IL-10, and TNF-α. TUNEL assay was used to detect apoptosis of pancreatic cells. The proteins p-Jak2 and p-Stat3 were investigated by Western blot.

Compared with the control group, pancreatic pathological score, pancreatic apoptosis, MDA, MPO, serum IL-1β, IL-6, and TNF-α levels were significantly higher in the AP group, and SOD levels were significantly decreased. Compared with the AP group, after treatment with alprostadil, AG490, and alprostadil+AG490, respectively, the pancreatic pathological score, apoptosis, MDA, MPO, serum IL-1β, IL-6, and TNF-α were significantly decreased in AP rats, while SOD levels were significantly increased. The protein levels of p-JAK2 and p-STAT3 were significantly upregulated in the AP group compared with the control group, and the protein levels of p-JAK2 and p-STAT3 after treatment with alprostadil, AG490, and alprostadil+AG490 were significantly decreased, and the effect of alprostadil+AG490 was the strongest.

Alprostadil can reduce pancreatic tissue damage, delay pancreatic cell apoptosis, and reduce inflammation and anti-oxidative stress by inhibiting the JAK2/STAT3 signal pathway, thus protecting the pancreas.