Efficacy of an Oxycodone-Propofol Combination versus a Fentanyl-Propofol Combination in Conscious Sedation during Therapeutic Endoscopic Retrograde Cholangiopancreatography in Elderly Patients.

BACKGROUND: With a rapidly aging population, the need for endoscopic retrograde cholangiopancreatography (ERCP) is increasing. The commonly used sedation anesthesia in ERCP is a combination of propofol and fentanyl, even though fentanyl may cause some adverse reactions such as respiratory depression. OBJECTIVES: This study aimed to evaluate the efficacy of oxycodone combined with propofol versus fentanyl combined with propofol for sedation anesthesia during ERCP. METHODS: A total of 193 patients aged from 65 to 80 years undergoing ERCP were enrolled and randomized into two groups: an "oxycodone combined with propofol" group (group OP, n = 97) and a "fentanyl combined with propofol" group (group FP, n = 96). The rate of perioperative adverse events as well as the recovery time, patients' satisfaction, and endoscopists' satisfaction were noted. RESULTS: There was no difference in the frequency of hypotension or bradycardia between the two groups, but there were more episodes of desaturation (SpO2 <90% for >10 s in 8.3%), postoperative nausea (7.3%), and vomiting (5.2%) in group FP than in group OP. Patients' satisfaction in group FP was lower than that in group OP. The recovery time was longer in group FP than in group OP. CONCLUSIONS: Oxycodone combined with propofol was effective in ERCP, with a low incidence of perioperative adverse events.

Real-Time Coseismic Displacement Retrieval Based on Temporal Point Positioning with IGS RTS Correction Products.

With the rapid development of the global navigation satellite system (GNSS), high-rate GNSS has been widely used for high-precision GNSS coseismic displacement retrieval. In recent decades, relative positioning (RP) and precise point positioning (PPP) are mainly adopted to retrieve coseismic displacements. However, RP can only obtain relative coseismic displacements with respect to a reference station, which might be subject to quaking during a large seismic event. While PPP needs a long (re)convergence period of tens of minutes. There is no convergence time needed in the variometric approach for displacements analysis standalone engine (VADASE) but the derived displacements are accompanied by a drift. Temporal point positioning (TPP) method adopts temporal-differenced ionosphere-free phase measurements between a reference epoch and the current epoch, and there is almost no drift in the displacement derived from TPP method. Nevertheless, the precise orbit and clock products should be applied in the TPP method. The studies in recent years are almost based on the postprocessing precise orbits and clocks or simulated real-time products. Since 2013, international GNSS service (IGS) has been providing an open-access real-time service (RTS), which consists of orbit, clock and other corrections. In this contribution, we evaluated the performance of real-time coseismic displacement retrieval based on TPP method with IGS RTS correction products. At first, the real-time precise orbit and clock offsets are derived from the RTS correction products. Then, the temporal-differenced ionosphere-free (IF) combinations are formed and adopted as the TPP measurements. By applying real-time precise orbit and clock offsets, the coseismic displacement can be real-timely retrieved based on TPP measurements. To evaluate the accuracy, two experiments including a stationary experiment and an application to an earthquake event were carried out. The former gives an accuracy of 1.8 cm in the horizontal direction and 4.1 cm in the vertical direction during the whole period of 15-min. The latter gives an accuracy of 1.2 cm and 2.4 cm in the horizontal and vertical components, respectively.

Serum levels of irisin predict short-term outcomes in ischemic stroke.

OBJECTIVE: Irisin is a 112-amino acid peptide found in rat and human skeletal muscle after exercise. Previous studies had suggested that higher circulating irisin levels were associated with an increased risk of vascular atherosclerosis and cardiovascular diseases. In this study, we determined irisin levels in serum, and investigated their associations with functional outcomes in a 3-month follow-up study in Chinese patients with first-ever acute ischemic stroke (AIS). METHODS: From September 2015 to December 2016, consecutive first-ever AIS patients admitted to the Department of Emergency of our hospital were identified. Serum irisin levels were measured at admission. Functional impairment was evaluated at discharge using the modified Rankin scale. The levels of irisin were expressed as median and interquartile ranges [IQR]. RESULTS: The irisin level was obtained in 324 patients (97.6%) with a median value of 291.2 ng/ml (IQR: 214.1-404.2 ng/ml). There were significantly negative correlations between levels of irisin and NHISS (r = -0.272; P < 0.001) and BMI (r = -0.193; P = 0.003). A poor functional outcome was found in 99 patients (30.6%; 95%CI: 25.5-35.6%). The poor functional outcome distribution across the irisin quartiles ranged between 51.9% (first quartile: Q1) to 12.4% (fourth quartile: Q4). In a multivariate model using the Q1 of irisin vs. Q2-4 together with the clinical variables, the marker displayed prognostic information and increased risk of poor outcomes by 94% (OR for Q1, 1.94 [95% CI, 1.19-3.42]; P = 0.018) and mortality 66% (OR for Q1, 1.66 [95% CI, 1.11-3.07]; P = 0.009). In addition, a model containing known risk factors plus irisin compared with a model containing known risk factors without irisin showed a greater discriminatory ability to predict poor outcomes (P = 0.01) and mortality (P = 0.02). CONCLUSIONS: A low serum irisin level is a predictor of poor early functional outcome in ischemic stroke patients. The underlying mechanisms of these associations remain to be investigated.

Ketamine ameliorates ischemia-reperfusion injury after liver autotransplantation by suppressing activation of Kupffer cells in rats.

This study aimed to investigate the protective effects of ketamine against hepatic ischemia-reperfusion (I/R) injury by suppressing activation of Kupffer cells (KCs) in rat liver autotransplantation. Male Sprague-Dawley rats were randomized into 3 groups (n = 10 each). Group I, the sham group, received saline. Group II received saline and underwent orthotopic liver autotransplantation (OLAT). Group III received 10 mg/kg ketamine and underwent OLAT. Blood samples were obtained at 3, 6, 12, and 24 h after I/R, and following ALT, AST, LDH, IL-6, TNF-α, IL-1ß, and IL-10 in serum were detected. Model rats were sacrificed at the indicated time points and the graft liver tissues were evaluated histologically. KCs were isolated from rat liver tissues, and inflammatory products and proteins of NF-κB signaling pathway were detected using quantitative RT-PCR and Western blotting. Our results showed that ketamine significantly decreased ALT, AST, LDH, IL-6, TNF-α, and IL-1ß levels and increased IL-10 level. Furthermore, ketamine alleviated the histopathology changes, by less KC infiltration and lower hepatocyte apoptosis. Moreover, activity of NF-κB signaling pathway in KCs was suppressed. In addition, production of pro- and anti-inflammatory factors is consistent with the results in tissues. Ketamine ameliorated I/R injury after liver transplantation by suppressing activation of KCs in rats.

Spatiotemporal reconstruction of global ocean surface pCO2 based on optimized random forest.

The partial pressure of ocean surface CO2 (pCO2) plays an important role in quantifying the carbon budget and assessing ocean acidification. For such a vast and complex ocean system as the global ocean, most current research practices tend to study the ocean into regions. In order to reveal the overall characteristics of the global ocean and avoid mutual influence between zones, a holistic research method was used to detect the correlation of twelve predictive factors, including chlorophyll concentration (Chlor_a), diffuse attenuation coefficient at 490 nm (Kd_490), density ocean mixed layer thickness (Mlotst), eastward velocity (East), northward velocity (North), salinity (Sal), temperature (Temp), dissolved iron (Fe), dissolved silicate (Si), nitrate (NO3), potential of hydrogen (pH), phosphate (PO4), at the global ocean scale. Based on measured data from the Global Surface pCO2 (LDEO) database, combined with National Aeronautics and Space Administration (NASA) Ocean Color satellite data and Copernicus Ocean reanalysis data, an improved optimized random forest (ORF) method is proposed for the overall reconstruction of global ocean surface pCO2, and compared with various machine learning methods. The results indicate that the ORF method is the most accurate in overall modeling at the global ocean scale (mean absolute error of 6.27µatm, root mean square error of 15.34µatm, R2 of 0.92). Based on independent observations from the LDEO dataset and time series observation stations, the ORF model was further validated, and the global ocean surface pCO2 distribution map of 0.25° × 0.25° for 2010 to 2019 was reconstructed, which is of significance for the global ocean carbon cycle and carbon assessment.

[Retracted] Methylene blue relieves the development of osteoarthritis by upregulating lncRNA MEG3.

[This retracts the article DOI: 10.3892/etm.2018.5918.].

Irisin improves BBB dysfunction in SAP rats by inhibiting MMP-9 via the ERK/NF-κB signaling pathway.

BACKGROUND: Blood-brain barrier (BBB) damage may lead to life-threatening pancreatic encephalopathy in patients with serious acute pancreatitis (SAP). Irisin alleviates BBB injury caused by cerebral ischemia-reperfusion by repressing matrix metalloproteinase-9 (MMP-9) expression. Serum levels of irisin are decreased in SAP patients. However, the role of irisin in BBB injury in SAP is still unknown. This study aimed to investigate whether irisin protects the BBB in SAP by affecting MMP-9 and its underlying regulatory mechanism. METHODS: An SAP model was established. Pancreatic injury was examined 24 h after SAP induction. Serum amylase and tumor necrosis factor-α (TNF-α) levels were examined by enzyme-linked immunosorbent assay (ELISA), and the brain water content was measured by the wet/dry proportion method. The structure and permeability of the BBB were examined by transmission electron microscopy, Evans blue exudation and transendothelial electrical resistance (TEER). RESULTS: In the brains of SAP rats, MMP-9 expression was increased, which was associated with damage to the BBB and the brain. Irisin inhibited this increase in MMP-9 and reduced brain edema and BBB permeability. The ERK/NF-κB axis is involved in irisin -mediated regulation of MMP-9. Irisin inhibited not only MMP-9 expression but also ERK/NF-κB phosphorylation. Furthermore, inhibiting ERK and NF-κB decreased MMP-9 levels and improved BBB dysfunction in SAP in vivo and in vitro. Moreover, irisin prevented the degradation of tight junctions (ZO-1, Claudin-5). The inhibition of ERK and NF-κB had similar effects on ZO-1 and Claudin-5 expression. CONCLUSION: Irisin protects tight junctions and alleviates BBB dysfunction in SAP by inhibiting MMP-9 expression and regulates MMP-9 expression through ERK/NF-κB phosphorylation.

Irisin Rescues Blood-Brain Barrier Permeability following Traumatic Brain Injury and Contributes to the Neuroprotection of Exercise in Traumatic Brain Injury.

Traumatic brain injury (TBI) has a high incidence, mortality, and morbidity all over the world. One important reason for its poor clinical prognosis is brain edema caused by blood-brain barrier (BBB) dysfunction after TBI. The mechanism may be related to the disorder of mitochondrial morphology and function of neurons in damaged brain tissue, the decrease of uncoupling protein 2 (UCP2) activity, and the increase of inflammatory reaction and oxidative stress. In this study, we aimed to investigate the effects of exogenous irisin on BBB dysfunction after TBI and its role in the neuroprotective effects of endurance exercise (EE) in mice. The concentrations of irisin in cerebrospinal fluid (CSF) and plasma of patients with mild to severe TBI were measured by ELISA. Then, male C57BL/6J mice and UCP2 knockout mice with C57BL/6J background were used to establish the TBI model. The BBB structure and permeability were examined by transmission electron microscopy and Evans blue extravasation, respectively. The protein expressions of irisin, occludin, claudin-5, zonula occludens-1 (ZO-1), nuclear factor E2-related factor 2(Nrf2), quinine oxidoreductase (NQO-1), hemeoxygenase-1 (HO-1), cytochrome C (Cyt-C), cytochrome C oxidase (COX IV), BCL2-associated X protein (Bax), cleaved caspase-3, and UCP2 were detected by western blot. The production of reactive oxygen species (ROS) was evaluated by the dihydroethidium (DHE) staining. The levels of inflammatory factors were detected by ELISA. In this study, we found that the CSF irisin levels were positively correlated with the severity of disease in patients with TBI and both EE and exogenous irisin could reduce BBB damage in a mouse model of TBI. In addition, we used UCP2-/- mice and further found that irisin could improve the dysfunction of BBB after TBI by promoting the expression of UCP2 on the mitochondrial membrane of neurons, reducing the damage of mitochondrial structure and function, thus alleviating the inflammatory response and oxidative stress. In conclusion, the results of this study suggested that irisin might alleviate brain edema after TBI by promoting the expression of UCP2 on the mitochondrial membrane of neurons and contribute to the neuroprotection of EE against TBI.

Exercise-Linked Irisin Prevents Mortality and Enhances Cognition in a Mice Model of Cerebral Ischemia by Regulating Klotho Expression.

Irisin, which can be released in the hippocampus after physical exercise, is demonstrated to have beneficial effects on neurovascular diseases. This study investigated the impact of exercise linked-irisin on mortality and cognition in a mice model of cerebral ischemia and further explored its underlying mechanism. The cerebrospinal concentrations of irisin and klotho from ischemic stroke patients were measured with an enzyme-linked immunosorbent assay (ELISA). The cognitive function of mice was evaluated by a series of behavioural experiments. The expressions of klotho, MnSOD, and FOXO3a in the hippocampus of mice were detected by Western blot. Superoxide production in the brain tissue of mice was evaluated with the dihydroethidium (DHE) dying. The results demonstrated that stroke patients showed a positive correlation between their CSF irisin concentration and klotho concentration. In addition, when mice subjected to cerebral ischemia, their cognitive function was impaired, the protein expressions of klotho, MnSOD, and FOXO3a downregulated, and the production of reactive oxygen species (ROS) increased compared with the sham group. After pretreatment with exogenous irisin, improved cognitive impairment, upregulated protein expressions of klotho, MnSOD, and FOXO3a, and reduced ROS generation were observed in mice with MCAO. However, the neuroprotective effects of irisin compromised with the evidence of severe cognitive impairment, decreased protein expressions of MnSOD and FOXO3a, and increased ROS production in klotho knockout mice. Thus, our results indicated that exercise-linked irisin could prevent mortality and improve cognitive impairment after cerebral ischemia by regulating klotho expression.

Quercetin improves blood-brain barrier dysfunction in rats with cerebral ischemia reperfusion via Wnt signaling pathway.

Reperfusion therapy after cerebral ischemia often leads to reperfusion injury which may cause brain edema and blood-brain barrier (BBB) dysfunction. As a natural bioflavonoid, quercetin may exert protective effects on BBB dysfunction. This study aimed to investigate effects of quercetin in a rat model of global cerebral ischemia reperfusion (I/R) injury and explore the potential mechanism. Male rats were randomly divided into 4 groups: sham group, I/R group, quercetin-treated group (25 µmol/kg twice daily for 3 consecutive days before I/R), and quercetin/DKK-1-treated group. Global cerebral I/R was induced by bilateral common carotid artery occlusion combined with hypotension for 20 min and reperfusion for 24 h. Neurological function was scored, and then rats were sacrificed. The brain was harvested for HE staining, NeuN staining, and detection of brain water content. The BBB structure and permeability were examined by transmission electron microscopy and Evans blue extravasation, respectively. The protein expression of MMP-9, ZO-1, Claudin-5, ß-catenin, and GSK-3ß, and the mRNA expression of Axin and LEF1 were detected in either the absence or presence of Wnt/ß-catenin inhibitor DKK-1. Results showed that quercetin reduced brain edema and BBB leakage, and improved BBB dysfunction. Quercetin could increase the expression of ZO-1, Claudin-5, ß-catenin, and LEF1, and decrease the expression of MMP-9, GSK-3ß and Axin. And all these protective effects of quercetin could be reversed by DKK-1. Thus, quercetin can alleviate BBB dysfunction after global cerebral I/R in rats and the mechanism may be related to the activation of canonical Wnt/ß-catenin signaling pathway.

Neuroprotective effects of irisin against cerebral ischemia/ reperfusion injury via Notch signaling pathway.

Irisin, a 112-amino acid peptide induced with exercise in mice and human is thought to have correlation with the short-term outcomes of patients in ischemic stroke. In the present study, the neuroprotective effects of irisin were evaluated in vivo and in vitro and its underlying mechanism was also explored. The global cerebral ischemia/reperfusion (I/R) model was established by bilateral common carotid artery occlusion for 20 min and reperfusion for 24 h in mice and oxygen-glucose deprivation/reperfusion in HT22 cells. Neurological function was scored and then the mice were sacrificed. The brains were harvested for HE staining and detection of brain water content (BWC). The percentage of neuronal apoptosis was evaluated by TUNEL and flow cytometry analysis. The mRNA expression of TNF-α and IL-1ß was detected by RT-PCR analysis. The Notch intracellular domain (NICD) was detected by double immunofluorescence staining and western blot, and the protein expression of Notch1 and Hes 1 was detected by western blot. It was observed that irisin could alleviate morphological damage and improve neurological function after global cerebral I/R injury in mice. The apoptosis of hippocampal neurons reduced in the presence of irisin in vivo and in vitro. Additionally irisin could downregulate the expression of IL-1ß and TNF-α and upregulate the expression of NICD, Notch1 and Hes 1 in vitro and in vivo. After the application of γ-secretase inhibitor DAPT, all the morphological, neurological and biochemical changes were reversed. Taken together, these results suggest that irisin could regulate the Notch signaling pathway that leads to the alleviation of transient global cerebral I/R injury.

Effects of irisin on the dysfunction of blood-brain barrier in rats after focal cerebral ischemia/reperfusion.

OBJECTIVE: To investigate whether irisin could protect against blood-brain barrier (BBB) dysfunction following focal cerebral ischemia/reperfusion in rats. METHODS AND MATERIALS: Seventy-two adult male Sprague Dawley rats weighing 280-320 g were randomly divided into three groups: sham operation group (S), focal cerebral ischemia/reperfusion group (FC), and irisin group (IR). Focal cerebral ischemia was induced by improved thread occlusion of right middle cerebral artery (MCAO) for 2 hr followed by reperfusion for 24 hr in rats. After 24 hr of reperfusion, the neurological evaluation was performed by the method of Longa's score. The histopathological changes were observed by HE staining. The brain water content was determined by detecting the wet weight and dry weight. The BBB permeability was assessed by fluorescence spectrophotometer and fluorescence microscopy for Evans blue (EB) extravasation. The activity and expression of matrix metalloproteinase-9 (MMP-9) in different groups were detected by immunohistochemical staining, Western blot, and gel gelatin zymography. RESULTS: After MCAO, the neurological deficit scores, the infarct volume, the brain water content, and the EB content were higher in the FC group than those in the S group (p < .05). While after irisin treatment, these indicators mentioned above were lower than those in the IR group (p < .05). Moreover, the protein expression of MMP-9 in the cortex increased significantly after MCAO, while irisin treatment could decrease the protein expression of MMP-9 in the cortex (p < .05). CONCLUSION: Our data suggest that irisin can attenuate brain damage both morphologically and functionally and protect BBB from disruption after focal cerebral ischemia/reperfusion, which is highly associated with the inhibition of the expression and activity of MMP-9 in the brain tissue.

Irisin alleviates pulmonary epithelial barrier dysfunction in sepsis-induced acute lung injury via activation of AMPK/SIRT1 pathways.

OBJECTIVE: Alveolar epithelial barrier dysfunction in response to inflammatory reaction contributes to pulmonary edema in acute lung injury(ALI).Irisin,a newly-found myokine,exerts the anti-inflammatory effects. This study aims to investigate the protective effects of irisin on lipopolysaccharide (LPS)-induced ALIin vivo and in vitro, and to explore its underlying mechanism. METHODS: Male SD rats and A549 cells were divided into 4 groups: control group, LPS group, Irisin pretreated group, and Irisin/Compound C(a special inhibitor of AMPK)-treated group. The ALI model was established by intravenous injection of LPS in rats, and LPS challenge in A549 cells. Pulmonary specimens were harvested for microscopic examination of the pathological changes, and the expression of AMPK,SIRT1,NF-κB, p66Shc and caspase-3 in lung tissues. The pulmonary permeability were examined by wet/dry lung weight ratio(W/D) and lung permeability index(LPI). The apoptotic index, and the expression of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), monocyte chemoattractant activating protein-1 (MCP-1), tight junctions (occludin,ZO-1) were determined both in lung tissue and A549 cells. RESULTS: Irisin alleviated lung histological changes and decreased pulmonary microvascular permeability in LPS-induced rats. Irisin up-regulated the expression of occludin, ZO-1,AMPK,SIRT1, down-regulated the expression of TNF-α,IL-1ß,MCP-1,NF-κB, p66Shc caspase-3, and decreased the apoptotic index in LPS-induced rats and A549 cells. All these protective effects of irisin could be reversed by Compound C. CONCLUSION: Irisin improved LPS-induced alveolar epithelial barrier dysfunction via suppressing inflammation and apoptosis, and this protective effect might be mediated by activating AMPK/SIRT1 pathways.

[Analysis of the fractal properties of the birth weight of Liangshan semi-fine wool sheep.].

Understanding of animal population genetic structure about quantitative traits is an important step in animal breeding. In the present study, the data of birth weight of the Liangshan semi-fine wool sheep was first studied by the fractal theory of nonlinear theory. The information dimension, correlation dimension, none-scale range, and the scale range were calculated. The results showed that (1) the information dimensions of the birth weight from 1996 to 2004 ranged from 0.66529 to 0.90675. The none-scale range and the range of the variation were very large. This indicates that the population had large dimensions of the BW (birth weight), large variation, and great potential in breeding; (2) the correlation dimensions ranged from 0.62438 to 0.86528, which indicates that the genetic structures of the population were highly correlated; (3) both of the two dimensions could reveal the fractal properties of the population genetic structure through two different aspects, and it was useful in studying the population genetic structure and animal breeding.

Hydroxybutyrate promotes the recovery from cerebral infarction by activating Amp-activated protein kinase signaling.

Recent studies have shown that hydroxybutyrate (GHB) is effective for protection against ischemia/brain damage in rat models. However, the specific underlying mechanism is poorly understood. In line with the previous studies, the present data showed that GHB improves cerebral blood flow (CBF) and physiological variables, including pH, pCO2 and pO2. Using CD31-immunofluorescence staining, a reduction of blood vessel density was indicated in the middle cerebral artery occlusion (MCAO) group; however, GHB treatment enhanced the cerebral vascular density in the ischemic area. In addition, GHB treatment increased the number of BrdU/lectin double-positive cells. Furthermore, the reduction of nestin-positive cells was identified in the brain of MCAO rats, while the number of nestin-positive cells was significantly increased after GHB administration. Compared with the sham group, the activation of Amp-activated protein kinase (AMPK) was identified in MCAO rats, suggesting stress-mediated AMPK activation after ischemia. Furthermore, the western blot assay showed that GHB treatment resulted in further activation of AMPK and endothelial nitric oxide synthase (eNOS), suggesting an enhanced energy supply. In summary, the present novel data indicates that GHB promotes the recovery from cerebral infarction mainly by activating AMPK and eNOS signaling, thereby enhancing angiogenesis and neuron regeneration.

Reduced peripheral blood miR-140 may be a biomarker for acute lung injury by targeting Toll-like receptor 4 (TLR4).

Acute lung injury (ALI) is a common complication of sepsis to which patients often succumb due to poor effective pharmacological interventions. Recent studies have focused on the potential application of circulating microRNAs (miRs or miRNAs) as novel prognostic and therapeutic biomarkers. The present study focuses mainly on miR-140, the role of which is poorly understood in the progression of ALI. The results of the present study revealed that toll-like receptor 4 (TLR4) expression was upregulated the lungs of rats with ALI. Meanwhile, serum levels of tumor necrosis factor-α, interleukin (IL)-6 and IL-1ß were significantly increased in rats with ALI compared with normal control rats. These data indicated the successful establishment of LPS-induced ALI. Furthermore, miR-140 was decreased in the peripheral blood of patients with ALI compared with control subjects. Receiver operator characteristic analysis indicated that miR-140 could be used to screen ALI patients and distinguish them from healthy controls. MiR-140 was demonstrated to be downregulated in the plasma and lungs of rats with ALI compared with the normal control group. A dual luciferase reporter assay indicated that TLR4 was a target gene of miR-140. To investigate whether miR-140 exerted its role via TLR4, a specific TLR4-targeting small interfering RNA was selected. It was revealed that TLR4 silencing was able to suppress the phosphorylation of NF-κB even in cells transfected with miR-140 inhibitor. In summary, reduced miR-140 expression and increased TLR4 signaling activation may serve a key role in the progression of ALI.

Methylene blue relieves the development of osteoarthritis by upregulating lncRNA MEG3.

Methylene blue (MB) is a long-term inhibitor of peripheral nerve axons, thereby alleviating or permanently eliminating pain. However, it remains unknown whether MB is safe and effective method of treating osteoarthritis (OA). MB was injected into the knee joints of rabbits and they were monitored for any histological structural changes. The results revealed no evident changes in the histological structure of the normal knee joint following injection of 1 mg/kg MB at 1, 4, 8 and 24 weeks post-injection. Compared with the vehicle control, MB treatment significantly enhanced the weight distribution and significantly decreased the swelling ratio of the rabbits. Additionally, levels of long non-coding RNA (lncRNA) maternally expressed 3 (MEG3) mRNA were significantly increased following treatment with MB, but the protein expression of P2X purinoceptor 3 (P2X3) was significantly suppressed compared with the vehicle control. The levels of interleukin (IL) 6, tumor necrosis factor (TNF)α, IL-1ß and IL-8 were significantly suppressed following MB treatment, indicating that MB protects against OA progression. It was also revealed that MEG3 overexpression significantly suppresses levels of P2X3 protein. ELISA indicated that the MEG3-induced reduction of IL-6, TNFα, IL-1ß and IL-8 expression was significantly reversed following P2X3 overexpression. Therefore, the results of the present study demonstrated that MB is an effective method of treating OA-associated pain by upregulating lncRNA MEG3 levels. Additionally, lncRNA MEG3 relieves the OA-associated pain and inflammation in a rabbit model of OA by inhibiting P2X3 expression.

Flurbiprofen axetil attenuates cerebral ischemia/reperfusion injury by reducing inflammation in a rat model of transient global cerebral ischemia/reperfusion.

Ischemic stroke has been ranked as the second cause of death in patients worldwide. Inflammation which is activated during cerebral ischemia/reperfusion (I/R) is an important mechanism leading to brain injury. The present study aimed to investigate the effect of flurbiprofen axetil on cerebral I/R injury and the role of inflammation in this process. Rats were subjected to sham operation or global cerebral I/R with or without flurbiprofen axetil (5 or 10 mg/kg). Global cerebral ischemia was achieved by occlusion of bilateral common carotid arteries combined with hypotension for 20 min followed by reperfusion for 72 h. Then the neurological deficit score, hippocampal cell apoptosis, levels of aquaporin (AQP) 4, AQP9, intercellular cell adhesion molecule-1 (ICAM-1), nuclear factor-κB (NF-κB), tumor necrosis factor (TNF-α), interleukin-1 ß (IL-1ß), thromboxane B2 (TXB2), and 6-keto-PGI1α were assessed. After reperfusion, neurological deficit score was significantly increased accompanied by severe neuronal damage (exacerbated morphological deficit, increased terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL)-positive cells and cleaved caspase-3 protein expression in hippocampal CA1 region). Cerebral I/R injury also enhanced expressions of TNF-α, IL-1ß, NF-κB, AQP4 and AQP9 as well as TXB2 and TXB2/6-keto-PGI1α. All these changes were reversed by pretreatment with flurbiprofen axetil. Flurbiprofen axetil protects the brain from cerebral I/R injury through reducing inflammation and brain edema.

Effects of Lipoxin A4 Pretreatment on Cognitive Function of Aged Rats after Global Cerebral Ischemia Reperfusion.

The aim of the present study was to investigate the effect of lipoxin A4 (LXA4) pretreatment on cognitive function of aged rats after global cerebral ischemia reperfusion, and to explore its possible mechanism. Thirty-six aged male Sprague-Dawley rats were randomly divided into three groups (n=2 each): sham-operation group (S group), global cerebral ischemia reperfusion group (I/R group) and LXA4-pretreatment group (L group). The rat model of global cerebral ischemia reperfüsion was established by occlusion of the bilateral common carotid artery with hypotension. The cognitive function of rats was determined by a step-down type passive avoidance test and Morris Water Maze test on the third day after reperfUsion. Rats were sacrificed after Water Maze test and the pathological changes of hippocampal CAI region were observed and the related inflammatory mediators were determined. As compared with S group, the escape latency in I/R group was prolonged from the first day to the fifth day, while that in L group was prolonged from the first day to the third day. The retention time in I/R group and L group in the first quadrant was shortened. The reaction time, frequency of reaction mistake and frequency of escape mistake in I/R group increased, and the latent period shortened. The frequency of escape mistake in L group increased, and the damage in the hippocampal CAI region of I/R group and L group was obvious. The levels of S-100ß, TNP-α, IL-lß, IL-10 and NF-κB in I/R group and L group increased. As compared with I/R group, the escape latency in L group was shortened from the first day to the fifth day, and the retention time in the first quadrant prolonged. The reaction time, frequency of reaction mistake and frequency of escape mistake in L group decreased, and the latent period prolonged. The damage in the hippocampal CAI region of L group was alleviated as well. The levels of S-100ß, TNP-α, IL-lß and NF-κB in L group decreased, and those of IL-10 increased. It can be concluded that LXA4 pretreatment can improve the cognitive function in aged rats after global cerebral ischemia reperfusion probably by inhibiting the inflammatory reaction.

miRNA-411 acts as a potential tumor suppressor miRNA via the downregulation of specificity protein 1 in breast cancer.

The expression and functions of microRNA (miR)-411 have been investigated in several types of cancer. However, until now, miR-411 in human breast cancer has not been examined. The present study investigated the expression, biological functions and molecular mechanisms of miR­411 in human breast cancer, discussing whether it offers potential as a therapeutic biomarker for breast cancer in the future. The expression levels of miR­411 in human breast cancer tissues and cells were measured using reverse transcription­quantitative polymerase chain reaction analysis. Following transfection with miR­411 mimics, an MTT assay, cell migration and invasion assay, western blot analysis and luciferase assay were performed in human breast cancer cell lines. According to the results, it was found that miR­411 was significantly downregulated in breast cancer, and associated with lymph node metastasis and histological grade. Additionally, it was observed that miR­411 suppressed cell growth, migration and invasion in the breast cancer cells. The present study also provided the first evidence, to the best of our knowledge, that miR­411 was likely to directly target specificity protein 1 in breast cancer. These findings indicated that miR­411 may be used a therapeutic biomarker for the treatment of breast cancer in the future.