Order transfer in a hybrid Raman-laser-optomechanical resonator.

Order is one of the most important concepts to interpret various phenomena such as the emergence of turbulence and the life-evolution process. The generation of laser can also be treated as an ordering process in which the interaction between the laser beam and the gain medium leads to the correlation between photons in the output optical field. Here, we demonstrate experimentally in a hybrid Raman-laser-optomechanical system that an ordered Raman laser can be generated from an entropy-absorption process by a chaotic optomechanical resonator. When the optomechanical resonator is chaotic or disordered enough, the Raman-laser field is in an ordered lasing mode. This can be interpreted by the entropy transfer from the Raman-laser mode to the chaotic motion mediated by optomechanics. Different order parameters, such as the box-counting dimension, the maximal Lyapunov exponent, and the Kolmogorov entropy, are introduced to quantitatively analyze this entropy transfer process, by which we can observe the order transfer between the Raman-laser mode and the optomechanical resonator. Our study presents a new mechanism of laser generation and opens up new dimensions of research such as the modulation of laser by optomechanics.

Pioglitazone Attenuates Lupus Nephritis Symptoms in Mice by Modulating miR-21-5p/TIMP3 Axis: the Key Role of the Activation of Peroxisome Proliferator-Activated Receptor-γ.

Lupus nephritis (LN) is a severe symptom of systemic lupus erythematosus and miR-21-5p is upregulated during LN. In the current study, the effects of pioglitazone (Pg), a peroxisome proliferator-activated receptor-γ (PPARγ) agonist, on LN development were assessed and explained by focusing miR-21-5p/TIMP3 axis. The expressions of miR-21-5p and PPARγ in LN mice were detected and then the mice were treated with pioglitazone to evaluate the anti-LN effects of agent. The miR-21-5p level was induced in MRL/lpr mice to confirm the central role of miR-21-5p inhibition in the protective effects of Pg against LN. The level of miR-21-5p was upregulated, while the level of PPARγ was downregulated in MRL/lpr mice. Pg inhibited miR-21-5p in renal tissues, which induced the expression of TIMP3. The changes in miR-21-5p/TIMP3 axis led to the improvements in renal structure and function, and inhibited autoimmune response. The induction of miR-21-5p impaired the effects of Pg, along with the suppression of TIMP3. The expression of miR-21-5p was associated with the progression of LN, contributing to the suppression of TIMP3 and development of LN. The inhibition of the miR-21-5p by Pg would restore the structure and function of kidneys in LN mice via the activation of PPARγ.

lncRNA ANRIL protects H9c2 cells against hypoxia-induced injury through targeting the miR-7-5p/SIRT1 axis.

BACKGROUND: Acute myocardial infarction (AMI) occurred in the heart, which underwent long-term ischemia, and was mainly caused by hypoxia. Recently, studies have uncovered the participation of long noncoding RNAs (lncRNAs) in the pathogenesis of heart disease. Here, we planned to probe the role and molecular basis of ANRIL in hypoxia-induced H9c2 cell injury. METHODS: Trypan blue exclusion assay and Transwell and flow cytometry assays were conducted to assess hypoxia-induced injury by determining the viability, migration, invasion, and apoptosis of H9c2 cells in different conditions, respectively. Gene expressions were evaluated by quantitative real-time polymerase chain reaction or western blot analysis as needed. RNA immunoprecipitation and luciferase reporter assays were applied to confirm the associations among genes. RESULTS: ANRIL expression was dramatically enhanced in hypoxia-injured H9c2 cells, and silencing ANRIL aggravated hypoxia-induced H9c2 cell injury. ANRIL positively regulated sirtuin 1 (SIRT1) expression via competitively binding with miR-7-5p. Moreover, inhibition of miR-7-5p counteracted ANRIL depletion-exacerbated injury in hypoxic H9c2 cells, meanwhile, forced SIRT1 expression attenuated the injury-promoting effect of miR-7-5p upregulation on hypoxic H9c2 cells. CONCLUSION: Our findings disclosed that ANRIL plays a protective part in hypoxia-induced H9c2 cell injury via modulating the miR-7-5p/SIRT1 axis, suggesting the great potential of ANRIL as a protective target for AMI.

Troxerutin attenuates myocardial cell apoptosis following myocardial ischemia-reperfusion injury through inhibition of miR-146a-5p expression.

The aim of the current study was to investigate the effects and the underlying mechanisms of troxerutin on myocardial cell apoptosis during ischemia-reperfusion (I/R) injury. Hypoxia/reoxygenation (H/R) model in neonatal rat cardiomyocytes, and I/R model in rats, were established following troxerutin preconditioning. The quantitative real-time polymerase chain reaction analysis was performed to examine the messenger RNA miR-146a-5p expression in cardiomyocytes and myocardial tissues. Hemodynamic parameters and serum creatine kinase, lactate dehydrogenase, tumor necrosis factor-α, and interleukin-10 were evaluated. Infarct size was examined by 2,3,5-triphenyltetrazolium chloride staining. Besides, myocardial apoptosis was detected by terminal deoxynucleotidyl transferase (dUTP) nick end labeling (TUNEL) assay. Western blot analysis was performed to determine the protein levels of caspase-3, Bax, and Bcl-2. The results showed that, troxerutin decreased rat cardiomyocyte apoptosis during H/R injury. Furthermore, the antiapoptotic effect of troxerutin against I/R injury was mediated by miR-146a-5p downregulation. In vivo experiments suggested that troxerutin alleviated myocardial I/R injury in rats via inhibition of miR-146a-5p. In conclusion, troxerutin exerted cardioprotective effects during I/R injury by downregulating miR-146a-5p.

Troxerutin Protects Against Myocardial Ischemia/Reperfusion Injury Via Pi3k/Akt Pathway in Rats.

BACKGROUND/AIMS: Troxerutin, also known as vitamin P4, has been commonly used in the treatment of chronic venous insufficiency (CVI) disease. However, its effect on in vivo myocardial ischemia/reperfusion (I/R) injury, a model that closely mimics acute myocardial infarction in humans, is still unknown. METHODS: The myocardial I/R injury rat model was created with troxerutin preconditioning. Myocardial infarct size was evaluated by the Evans blue-TTC method. Hemodynamic parameters, including the heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), maximal rate of rise in blood pressure in the ventricular chamber (+dp/dt max), and maximal rate of decline in blood pressure in the ventricular chamber (-dp/dt max) were monitored. Serum TNF-α and IL-10 were determined by ELISA kit. Cell apoptosis was detected by MTT method. RESULTS: Troxerutin preconditioning significantly reduced myocardial infarct size, improved cardiac function, and decreased the levels of creatine kinase (CK), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in the I/R injury rat model. The serum and mRNA levels of TNF-α and IL-10 as well as some apoptosis markers (Bax, Caspase 3) also decreased. Moreover, troxerutin pretreatment markedly increased the phosphorylation of Akt, and blocking PI3K activity by LY294002 abolished the protective effect of troxerutin on I/R injury. CONCLUSION: Troxerutin preconditioning protected against myocardial I/R injury via the PI3K/Akt pathway.

Upregulation of miR-21 by Ghrelin Ameliorates Ischemia/Reperfusion-Induced Acute Kidney Injury by Inhibiting Inflammation and Cell Apoptosis.

Renal ischemia-reperfusion (I/R) injury can be caused by cardiac surgery, renal vascular obstruction, and kidney transplantation, mainly leading to acute kidney injury (AKI), which is complicated by lack of effective preventative and therapeutic strategies. Ghrelin has recently been reported to possess anti-inflammatory properties in several types of cells; however, little attention has been given to the role of ghrelin in I/R-induced AKI. The aim of this study is to explore the role of ghrelin in I/R-induced AKI. In this study, an I/R-induced rat AKI model and a hypoxia-induced NRK-52E cell I/R model were successfully constructed. Ghrelin expression was increased significantly in these rat and cell models. After enhancing ghrelin level by injecting exogenous ghrelin into rats or transfecting a ghrelin-pcDNA3.1 vector into renal tubular epithelial cells, we observed that I/R-induced AKI can be ameliorated by ghrelin, as shown by alterations in histology, as well as changes in serum creatinine (SCr) level, cell apoptosis, and the levels of inflammatory factors. Based on the importance of microRNA-21 (miR-21) in renal disease and the modulation effect of ghrelin on miR-21 in gastric epithelial cells, we tested whether miR-21 participates in the protective effect of ghrelin on I/R-induced AKI. Ghrelin could upregulate the PI3K/AKT signaling pathway by increasing the miR-21 level, which led to the protective effect of ghrelin on I/R-induced AKI by inhibiting the inflammatory response and renal tubular epithelial cell apoptosis. Our research identifies that ghrelin can ameliorate I/R-induced AKI by upregulating miR-21, which advances the understanding of mechanisms by which ghrelin ameliorates I/R-induced AKI.

Modulation of HERG K+ channels by chronic exposure to activators and inhibitors of PKA and PKC: actions independent of PKA and PKC phosphorylation.

BACKGROUND: Human ether-a-go-go-related gene (HERG) channel is the major molecular component of the native rapid delayed rectifier K(+) current (IKr) that is a crucial determinant of cardiac repolarization. Impairment of IKr/HERG function is commonly believed to be a mechanism causing long QT syndromes (LQTS), a lethal ventricular tachyarrhythmia. The cAMP-dependent protein kinase A (PKA) and PKC activities are markedly increased in some pathological conditions of the heart such as heart failure. This study was designed to investigate the effects of acute and chronic exposure to PKA or PKC activators and inhibitors on HERG channel activities and to provide insight into the mechanisms for the modulations. METHODS: Channel activity was measured in HEK293 cells stably expressing HERG using whole-cell patch-clamp techniques. Intracellular reactive oxygen species (ROS) were measured by CM-H2DFDA. Mitochondrial membrane potential (ΔΨm) was measured using JC-1 dye. HERG channel phosphorylation was assayed by [(32)P]orthophosphate methods. RESULTS: Acute exposure of cells to PKA or PKC activators by bath superfusion minimally affected IHERG, and so did the PKA or PKC inhibitor. By comparison, prolonged exposure (chronic incubation) of cells to PKA or PKC activators significantly impaired HERG K(+) channel function as reflected by reduced IHERG density and positive shift of the steady-state activation curve. Antioxidants vitamin E and MnTBAP both abolished the depressive effects of PKA or PKC activators on HERG function. Further, both PKA and PKC activators stimulated production of intracellular reactive oxygen species (ROS), an effect efficiently prevented by antioxidants or by PKA and PKC inhibitors. CONCLUSIONS: HERG function is insensitive to PKA or PKC phosphorylation modulation per se, but can be impaired by the activators of PKA or PKC with long exposure likely via generation of ROS. In view of the critical role of HERG K(+) channel in regulating cardiac repolarization and the sustained activation of both PKA and PKC in many pathological conditions of the heart such as heart failure, it is conceivable that HERG impairment by ROS accumulation induced by PKA and PKC contributes to the impaired cardiac repolarization.

[Risk factors of contrast-induced nephropathy in patients after coronary artery intervention].

OBJECTIVE: To explore the risk factors of contrast-induced nephropathy (CIN) in patients after coronary artery intervention. METHODS: A total of 637 patients undergoing diagnostic coronary angiography or percutaneous coronary intervention were enrolled. They were divided into the CIN and non-CIN groups according to the changes in serum creatinine levels within 48 hours after coronary artery intervention. Then the relevant risk factors of CIN were analyzed. RESULTS: Among them, CIN occurred in 49 patients with an incidence of 7.7%. The patients with diabetes and renal insufficiency had higher incidence of CIN at 15.5% and 22.5% respectively. Logistic regression analysis showed that the risk factors of CIN included advanced age, smoking, diabetes, renal insufficiency, hypercholesterolemia and hyperuricemia. CONCLUSION: For the patients of coronary artery intervention, the major risk factors of CIN are advanced age, diabetes and renal insufficiency.