Irisin Prevents Cell Death in High Glucose via NLRP3 Inhibition.

Background: Impaired cardiac microvascular function has been implied in the pathophysiology of diabetic cardiovascular disease. However, the specific mechanism remains to be determined. Pyroptosis is a type of cell death that differs from apoptosis and autophagy. It is caused by the formation of plasma membrane pores through amino-terminal fragments of Gasdermin D (GSDMD), leading to the secretion of IL-1ß and IL-18. Recent studies have shown that irisin, a myokine cleaved by the extracellular domain of FNDC5, plays a protective role in cardiovascular diseases. Here, we investigated the potential role of pyroptosis on the cardiac microvascular endothelial cells (CMECs) injury induced by high glucose (HG) and further determined the protective effect of irisin on pyroptosis. Methods: CMECs were cultured with normal glucose (control group, 5.5 mM) and high glucose (25 mM) medium for 12, 24, and 48 h respectively. The pyroptosis of CMECs was measured by immunofluorescence staining, ELISA, and Western blot assays. Moreover, the apoptosis level was determined by flow cytometry and TUNEL staining. Results: Our results showed that HG promoted apoptosis and pyroptosis. However, irisin reversed the increased apoptosis and pyroptosis. To investigate the underlying mechanism, we overexpressed the NLRP3 protein. We found the protective effect of irisin on apoptosis and pyroptosis was abolished by NLRP3 over-expression. Conclusions: Our data suggest that irisin protects CMECs against apoptosis and pyroptosis, at least in part, by inhibiting NLRP3 inflammasome.

Irisin-pretreated BMMSCs Secrete Exosomes to Alleviate Cardiomyocytes Pyroptosis and Oxidative Stress to Hypoxia/reoxygenation Injury.

BACKGROUND: The cardiomyocytes pyroptosis and bone marrow-derived mesenchymal stem cells have been well considered as novel therapies to attenuate myocardial ischemia/reperfusion injury, however, the relationship has not yet been determined. OBJECTIVE: We aim to evaluate whether pre-treatment bone marrow-derived mesenchymal stem cells protect against myocardial ischemia/reperfusion injury by repressing cardiomyocytes pyroptosis, as well as to further elucidate the potential mechanisms. METHODS: Cardiomyocytes were treated with hypoxia, followed by reoxygenation to mimic myocardial ischemia/reperfusion injury. Pre-treatment bone marrow-derived mesenchymal stem cells or their exosomes were co-cultured with cardiomyocytes following hypoxia/reoxygenation. Cell Counting Kit-8 assay was used to determine cell viability. Reactive oxygen species production was determined by dihydroethidium stain. Enzyme-linked immunosorbent assays were used to detect IL-1ß and IL-18. RESULTS: We observed that Irisin pre-treatment bone marrow-derived mesenchymal stem cells protected cardiomyocytes against hypoxia/reoxygenation-induced injuries. The underlying molecular mechanism was further identified. Irisin-BMMSCs were found to secrete exosomes, which repressed cardiomyocytes pyroptosis and oxidative stress response by suppressing NLRP3 under hypoxia/reoxygenation conditions. CONCLUSION: Based on our findings, we revealed a promising target that exosomes derived from bone marrow-derived mesenchymal stem cells with Irisin treatment to elevate the therapeutic benefits for hypoxia/ reoxygenation injury.

FNDC5/irisin reduces ferroptosis and improves mitochondrial dysfunction in hypoxic cardiomyocytes by Nrf2/HO-1 axis.

Myocardial infarction is characterized by cardiomyocyte death and mitochondrial dysfunction induced by ischemia. Ferroptosis, a novel form of cell death, has been found to play critical roles under ischemic conditions. Recently, several studies have shown that fibronectin type III domain-containing 5 (FNDC5) and its cleaved form, irisin, protect the heart against injury. However, its protective effect on ferroptosis and mitochondrial impairments is still unclear. Thus, our aim was to investigate the role of irisin in ferroptosis and mitochondrial dysfunction in cardiomyocytes under hypoxic conditions. Cardiomyocytes were treated with FNDC5 overexpression and/or irisin under normoxic and hypoxic conditions. Cell viability was assessed by Cell Counting Kit-8 assay. Reactive oxygen species production was evaluated by dihydroethidium staining. In addition, the intracellular ferrous iron level (Fe2+ ) and the relative concentration of malondialdehyde and ATP content were determined using an Iron Assay Kit, Lipid Peroxidation Assay Kit, and ATP Bioluminescent Assay Kit. The superoxide dismutase level in cells was measured using an Enzyme-Linked Immunosorbent Assay Kit. Furthermore, an immunoblotting assay was used to determine ferroptosis-related mitochondrial proteins. Hypoxia promoted cell death, increased ferroptosis, and caused mitochondrial dysfunction in cardiomyocytes. Interestingly, FNDC5 overexpression and/or irisin administration elevated cell viability, decreased ferroptosis, and reversed mitochondrial impairments induced by hypoxia. Mechanistically, FNDC5/irisin reduced ferroptosis and reversed mitochondrial impairments by Nrf2/HO-1 axis in hypoxic cardiomyocytes. Thus, we have demonstrated that FNDC5/irisin plays a protective role in ferroptosis and mitochondrial dysfunction in hypoxia-induced cardiomyocytes.

Unsupervised Video Matting via Sparse and Low-Rank Representation.

A novel method, unsupervised video matting via sparse and low-rank representation, is proposed which can achieve high quality in a variety of challenging examples featuring illumination changes, feature ambiguity, topology changes, transparency variation, dis-occlusion, fast motion and motion blur. Some previous matting methods introduced a nonlocal prior to search samples for estimating the alpha matte, which have achieved impressive results on some data. However, on one hand, searching inadequate or excessive samples may miss good samples or introduce noise; on the other hand, it is difficult to construct consistent nonlocal structures for pixels with similar features, yielding video mattes with spatial and temporal inconsistency. In this paper, we proposed a novel video matting method to achieve spatially and temporally consistent matting result. Toward this end, a sparse and low-rank representation model is introduced to pursue consistent nonlocal structures for pixels with similar features. The sparse representation is used to adaptively select best samples and accurately construct the nonlocal structures for all pixels, while the low-rank representation is used to globally ensure consistent nonlocal structures for pixels with similar features. The two representations are combined to generate spatially and temporally consistent video mattes. We test our method on lots of dataset including the benchmark dataset for image matting and dataset for video matting. Our method has achieved the best performance among all unsupervised matting methods in the public alpha matting evaluation dataset for images.

Tai chi for overweight/obese adolescent and young women with polycystic ovary syndrome: study protocol for a randomized controlled trial.

BACKGROUND: Tai Chi is a moderately intense exercise that dates back to ancient China. It has been reported that Tai Chi not only has beneficial effects on metabolic disorders, such as diabetes, cardiovascular diseases and obesity, but also has favorable effects on psychological well-being. Since these conditions are quite closely associated with polycystic ovary syndrome (PCOS), we hypothesis that Tai Chi could be a potential treatment option for PCOS patients. We aim to determine the feasibility and effectiveness of Tai Chi on overweight/obese adolescent and young women with PCOS. METHODS: A total of 50 patients will be randomized into two arms: (1) Tai Chi or (2) self-monitored exercise. Both groups will exercise for 3 months. The primary hypothesis is that Tai Chi results in a significantly lower Body Mass Index (BMI) than self-monitored exercise. The study was approved by the Ethics Committee of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine. DISCUSSION: This is the first study to determine the feasibility and effectiveness of Tai Chi in treating overweight/obese adolescent and young women with PCOS. The trial will provide evidence to assess the feasibility of a future multicenter, randomized controlled trial. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02608554 . Registered on 17 November 2015.