Knockdown of p66ShcA activates Nrf2 pathway to protect cardiomyocytes from oxidative stress and inflammation induced by H2O2.

OBJECTIVE: Oxidative stress and inflammation are the most common causes of myocardial ischemia and hypoxia. This article focuses on the effect of p66ShcA on H2O2-induced cardiomyocytes. MATERIALS AND METHODS: The p66ShcA knockdown model of H9c2 cells was constructed by plasmid transfection. After treatment of different groups with H2O2, oxidative stress-related factors and inflammatory factors were detected. RESULTS: The expressions of SOD1, SOD2, GPX1, and GPX3 in H2O2 cells were significantly decreased, IL-1ß and IL-6 expression were significantly increased, while p66ShcA siRNA negative group could promote the expression of SOD1, SOD2, GPX1, and GPX3, inhibit the expression of IL-1ß and IL-6 significantly, and activates the Keap1/Nrf2 pathways. CONCLUSIONS: Knockdown of p66ShcA can activate Keap1/Nrf2 pathway, which inhibits H2O2-induced oxidative stress and inflammation in H9c2 cells.

Multi-scale mechanical investigation of articular cartilage suffered progressive pseudorheumatoid dysplasia.

BACKGROUND: Progressive pseudorheumatoid dysplasia is a rare skeletal dysplasia mainly caused by abnormal autosomal recessive inheritance. Although the main function of cartilage is mechanical support and the characteristics of this disease is the degradation of AC, previous studies on it had been mainly focused on clinical and genetic aspects and the mechanical behavior of the cartilage affected by PPRD is still ambiguous. In this study, we investigate the mechanics and structure of the cartilage suffered disease at multi-scale, from individual chondrocytes to the bulk-scale tissue. METHODS: Depth-sensing indenter were employed to investigate the mechanics of cartilage; we performed atomic force microscope nanoindentation to investigate the cell mechanics and scanning electron microscopy were used to explore the structure feature and chemical composition. FINDINGS: The elastic modulus of chondrocytes harvested from cartilage suffered from progressive pseudorheumatoid dysplasia is significantly higher than from normal cartilage, same trend were also found in tissue level. Moreover, denser collagen meshwork and matrix calcification were also observed. INTERPRETATION: The elastic modulus of cartilage should closely related to its denser structure and the calcification, and may potentially be an indicator for clinical diagnosis. The stiffening of chondrocytes during PPRD progression should play a rather important role in its pathogenesis.

PCL/EUG scaffolds with tunable stiffness can regulate macrophage secretion behavior.

Osteoarthritis (OA) is a prevalent joint disorder worldwide. Recent studies suggested that macrophages play an important role in the progression of OA. However, the detailed pathology related to macrophages is still ambiguous, especially where related to mechanotransduction. In this study, polycaprolactone (PCL) and Eucommia Ulmoides Gum (EUG) composite scaffolds were first fabricated by electrospinning. The stiffness of as-fabricated scaffolds was altered by adjusting the PCL-to-EUG ratio. The mechanical properties, structural characteristics and chemical composition of the scaffolds were investigated using various materials characterization techniques. The results show that stiffness of the scaffolds was in the same range as that of cartilage tissues with OA. Confocal microscopy and reverse transcription-polymerase chain reaction (RT-PCR) were performed to investigate the macrophages cultured on the scaffolds. Significant morphological changes of cells were observed on PCL/EUG scaffolds with different stiffness. The expression of inflammatory and fibrosis-related cytokines increases as scaffold stiffness decreases, similar to the trend observed in OA progression.

Long non-coding RNA H19 protects acute myocardial infarction through activating autophagy in mice.

OBJECTIVE: We investigate the effect of long non-coding RNA H19 in acute myocardial infarction (AMI) and the underlying mechanism. MATERIALS AND METHODS: C57BL/6 mice were subjected to AMI and injected with lentivirus pcDNA-H19. After AMI procedures for 3 weeks, cardiac function was detected by echocardiography. The infarct size was stained by triphenyltetrazolium chloride. H19 expression in mice was measured by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Protein expressions of LC3, Beclin-1, and ATG-7 in mice were measured by Western blot. RESULTS: Our results indicated that H19 expression was significantly downregulated in the infarcted myocardium. Overexpression of H19 after injection with pcDNA-H19 in mice could reduce infarct size and improve cardiac function through upregulating the ratio of LC3-II/I and expressions of Beclin-1 and ATG-7. CONCLUSIONS: Overexpression of H19 could protect AMI in mice via activating autophagy.

WITHDRAWN: PCL/EUG scaffolds with tunable stiffness can regulate macrophage secretion behavior.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.pbiomolbio.2018.05.008. The duplicate article has therefore been withdrawn.

Analysis on application timing of IABP in emergency PCI treatment of patients with combined acute myocardial infarction and cardiac shock.

OBJECTIVE: To study the application timing and effect of intra-aortic balloon pump (IABP) in the emergency PCI treatment of patients with combined acute myocardial infarction (AMI) and cardiogenic shock (CS). PATIENTS AND METHODS: 84 cases of patients with combined AMI and CS under PCI in emergency treatment were randomly divided into the control group (n=42) and observational group (n=42). The control group underwent IABP again, after the invalidation of internal medicine drug treatment, while the observational group underwent IABP before the operation. We compared the effects of treatment. RESULTS: After the intervention, the averages of arterial pressure and urine volume were increased in both groups than before (p <0.05). The average of heart rate was decreased, and the improvement in the observational group was more significant (p <0.05). However, the mortality rate in the observational group during the perioperative period was decreased than the control group as well as, the success rate of off-respirator was significant (p <0.05). The comparison of IABP complication occurrence rate as well as the survival rate after 1-year follow-up between both groups was not significantly different. Additionally, whereas the NYHA grouping in two groups was gradually improved, the difference was not statistically significant between both groups. However, in the observational group, the LVEF after one-month follow-up was significantly higher than in the control group (p <0.05), but not when comparing 1-year. VEDd at each time point in two groups were also similar. CONCLUSIONS: The early IABP can improve hemodynamics of patients with combined AMI and CS under emergency PCI. It can reduce perioperative mortality rate, improve the success rate of off-respirator, but cannot increase IABP complication incidence rate while having little influence on the long-term survival rate and cardiac function indicator.

Curative effect and safety of intrathecal transplantation of neural stem cells for the treatment of cerebral hemorrhage.

In this study, we aimed to explore the curative effect and safety of neural stem cell intrathecal transplantation for the treatment of cerebral hemorrhage. We transplanted 4.0 x 10(8) neural stem cells per procedure into the subarachnoid space by lumbar puncture 7 days after cerebral hemorrhage, twice a week, a total of 4 times. NIHSS scores and brain CT scans were conducted to assess neural functions and the volume of perihematoma lesions in patients on days 1, 7, 14, 21, and 28. We found that the NIHSS scores and the volume of the perihematoma lesions were significantly reduced after day 14. The differences before and after treatment were highly significant in intra- and between-group comparisons (P < 0.05). There were no adverse reactions, except for transient fever and shivering in a few patients. Our data suggest that the use of neural stem cells in intrathecal transplantation for the treatment of cerebral hemorrhage is safe and effective.

Contemporary management of atrial fibrillation: a brief review.

Atrial fibrillation (AF) is the most common cardiac arrhythmia with a prevalence of up to 10% in patients who are 80 years and older. There has been some significant progress in the understanding and management of AF in recent years. Large-scale clinical trials have provided solid evidence in supporting the role of anti-thrombotic therapies in the prevention of stroke in moderate to high risk patients. Appropriate control of the ventricular rate or the maintenance of sinus rhythm offers long-term benefits in specific groups of patients. Catheter ablation or "Maze" surgery has proven to be curative to some patients. However, the implementation of the evidence-based therapeutic strategies in the day-to-day care of the AF patients have been found to vary greatly from one institution to another, some of which are hindering the achievement of optimal long-term outcomes. In this brief review, some of the key strategies in the evidence-based management of AF are discussed, with particular emphasis on anti-thrombotic therapy, rhythm or rate control, as well as catheter ablation.