Damlynge0096

The link between tendon stem/progenitor cells (TSPCs) senescence and tendon aging has been well recognized. However, the cellular and molecular mechanisms of TSPCs senescence are still not fully understood. Inflammation chemical In present study, we investigated the role of Aquaporin 1 (AQP1) in TSPCs senescence. We showed that AQP1 expression declines with age during tendon aging. In aged TSPCs, overexpression of AQP1 significantly attenuated TSPCs senescence. In addition, AQP1 overexpression also restored the age-related dysfunction of self-renewal, migration and tenogenic differentiation. Furthermore, we demonstrated that the JAK-STAT signaling pathway is activated in aged TSPCs, and AQP1 overexpression inhibited the JAK-STAT signaling pathway activation which indicated that AQP1 attenuates senescence and age-related dysfunction of TSPCs through the repression of JAK-STAT signaling pathway. Taken together, our findings demonstrated the critical role of AQP1 in the regulation of TSPCs senescence and provided a novel target for antagonizing tendon aging.BACKGROUND Management of incessant electrical storm is poorly defined. These 2 case studies demonstrate a simplified percutaneous approach to achieve stellate ganglion ablation (SGA) and to promptly control malignant ventricular arrhythmias. CASE REPORT This report describes 2 patients with deteriorating hemodynamics, progressive ventricular arrhythmias, and worsening heart failure, managed with emergent percutaneous fluoroscopically-guided bilateral SGA to achieve bilateral cardiac sympathetic denervation. While supine and intubated, the left and then right stellate ganglion were identified guided by anatomic landmarks. Using a 22-guage, 3.5-inch spinal needle, contrast dye was injected with appropriate outline of the stellate ganglion at the uncinate process of the C6 vertebra. Bupivacaine 0.5% was injected, followed by phenol 6%. Successful SGA was confirmed by intentional Horner's syndrome with bilateral eye lag. The procedures were completed in about 30 min without complications and there was a dramatic reduction in ventricular arrhythmias. link2 CONCLUSIONS Emergent percutaneous bilateral SGA can be accomplished with a brief procedure resulting in management of electrical storm.BACKGROUND Freshly isolated mouse embryonic fibroblasts (MEFs) have great proliferation capacity but quickly enter senescent state after several rounds of cell cycle, a process called premature senescence. Cellular senescence can be induced by various stresses such as telomere erosion, DNA damage, and oncogenic signaling. But the contribution of other molecules, such as growth factors, to cellular senescence is incompletely understood. This study aimed to compare the gene expression difference between non-senescent and senescent MEFs to identify the key molecule(s) involved in the spontaneous senescence of MEFs. MATERIAL AND METHODS Primary MEFs were isolated from E12.5 pregnant C57/BL6 mice. The cells were continuously cultured in Dulbecco's Modified Eagle Medium for 9 passages. SA-ß-Gal staining was used as an indicator of cell senescence. The supernatant from primary MEFs (P1 medium) or Passage 6 MEFs (P6 medium) were used to culture freshly isolated MEFs to observe the effects on cell senescence state. Gene expression profiles of primary and senescent MEFs were investigated by RNA-Seq to find the key genes involved in cell senescence. Adipocyte differentiation assay was used to evaluate the stemness of MEFs cultured in FGF2-stimulated medium. RESULTS The senescence of MEFs cultured in the P1 medium was alleviated when compared to the P6 medium. Downregulation of FGF2 expression was revealed by RNA-Seq and further confirmed by real-time quantitative polymerase chain reaction and western blot. FGF2-stimulated medium also had anti-senescence function and could maintain the differentiation ability of MEFs. CONCLUSIONS The premature senescence of MEFs was at least partially caused by FGF2 deficiency. Exogenous FGF2 could alleviate the senescent phenotype.High fat diet (HFD) treated mouse is widely used as experimental animal model for hyperlipidemia and hyperglycemia study. Many factors contribute to establish animal model that meant to simulate high fat and glucose diet induced phenotypes. In the present study, four strains of experiment mouse treated by HFD were used to explore the impact of mouse strain on lipid profile, glucose level, and major inflammation cytokines. HFD fed Kunming and ICR mouse gained significantly higher body weight than control which was not shown by C57BL/6 and BALB/c mouse. All four strains fed by HFD has heavier liver and adipose tissue than control ones. Obvious fat droplets and enlarged adipose cells were observed in obese mouse of four strains. Additionally, obese mouse showed typical response to glucose and insulin load in OGTT and ITT. Serum TC, LDL-c, and TC/HDL-c ratio, but not TG, increased in all four strains. Major inflammatory cytokines and insulin level showed little changes in obese mouse as well (P less then 0.05) The present study could provide basic information for diet induced obesity developed by four commonly used experimental mouse strains.BACKGROUND Prompt and potent antiplatelet effects are important aspects of management of ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). We evaluated the association between platelet-derived thrombogenicity during PPCI and enzymatic infarct size in STEMI patients.Methods and ResultsPlatelet-derived thrombogenicity was assessed in 127 STEMI patients undergoing PPCI by (1) the area under the flow-pressure curve for the PL-chip (PL18-AUC10) using the total thrombus-formation analysis system (T-TAS); and (2) P2Y12reaction units (PRU) using the VerifyNow system. Patients were divided into 2 groups (High and Low) based on median PL18-AUC10during PPCI. PRU levels during PPCI were suboptimal in both the High and Low PL18-AUC10groups (median [interquartile range] 266 [231-311] vs. 272 [217-317], respectively; P=0.95). The percentage of final Thrombolysis in Myocardial Infarction (TIMI) 3 flow was lower in the High PL18-AUC10group (75% vs. 90%; P=0.021), whereas corrected TIMI frame count (31.3±2.5 vs. 21.0±2.6; P=0.005) and the incidence of slow-flow/no-reflow phenomenon (31% vs. 11%, P=0.0055) were higher. The area under the curve for creatine kinase (AUCCK) was greater in the High PL18-AUC10group (95,231±7,275 IU/L h vs. 62,239±7,333 IU/L h; P=0.0018). Multivariate regression analysis identified high PL18-AUC10during PPCI (β=0.29, P=0.0006) and poor initial TIMI flow (β=0.37, P less then 0.0001) as independent determinants of AUCCK. CONCLUSIONS T-TAS-based high platelet-derived thrombogenicity during PPCI was associated with enzymatic infarct size in patients with STEMI.BACKGROUND To take full advantage of transesophageal echocardiography (TEE) during cardiopulmonary resuscitation (CPR), we propose a flowchart derived from representative cases.Methods and ResultsTEE was used in patients requiring CPR to obtain information potentially helpful for rescue. TEE navigated the CPR procedures (navigation TEE), identified the possible cause of arrest (focus TEE), and optimized treatment while checking for pitfalls (secure TEE). In addition, TEE corrected prehospital misdiagnoses and detected new complications caused by CPR. CONCLUSIONS TEE provides valuable information without interrupting CPR procedures. It is hoped that our flowchart may facilitate goal-directed, efficient assessment.The feasibility of the 3D dynamic improved motion-sensitized driven-equilibrium steady-state free precession (3D dynamic iMSDE SSFP) was evaluated for visualizing CSF motion and the appropriate parameters were determined. Both flow phantom and volunteer studies revealed that linear ordering and the shortest acquisition duration time were optimal. 3D dynamic iMSDE SSFP provides good quality imaging of CSF motion in the whole brain and enables visualization of flow in arbitrary planes from a single 3D volume scan.Cytisine N-methylene-(5,7-dihydroxy-4'-methoxy)-isoflavone (CNF2) is a new compound isolated from the Chinese herbal medicine Sophora alopecuroides. Preliminary pharmacodynamic studies demonstrated its activity in inhibiting breast cancer cell metastasis. This study examined the pharmacokinetics, absolute bioavailability, and tissue distribution of CNF2 in rats, and combined computer-aided technology to predict the druggability of CNF2. The binding site of CNF2 and the breast cancer target HER2 were examined with molecular docking technology. Next, ACD/Percepta software was used to predict the druggability of CNF2 based on the quantitative structure-activity relationship (QSAR). Finally, a simple and effective high-performance liquid chromatography (HPLC) method was used to determine plasma pharmacokinetics and tissue distribution of CNF2 in rats. Prediction and experimental results show that compared with the positive control HER2 inhibitor SYR127063, CNF2 has a stronger binding affinity with HER2, suggesting that its efficacy is stronger; and the structure of CNF2 complies with the Lipinski's Rule of Five and has good drug-likeness. The residence time of CNF2 in rats is less than 4 hours, and the metabolic rate is relatively fast; But the absolute bioavailability of CNF2 in rats was 6.6%, mainly distributed in the stomach, intestine, and lung tissues, where the CNF2 contents were 401.20 μg/g, 144.01 μg/g, and 245.82 μg/g, respectively. This study constructed rapid screening and preliminary evaluation of active compounds, which provided important references for the development and further research of such compounds.The neurodevelopmental toxicity of isoflurane has been proved by many studies, which makes it essential to explore the underline mechanisms and search for protective agents to attenuate its neurotoxcity. Accumulating evidence showed that L-theanine had neuroprotective effects on injured neurons and the developing brain. The present study was designed to investigate whether L-theanine could attenuate isoflurane-induced damage in neural stem cells and cognitive impairment in young mice, and to discuss the role of Akt/GSK-3β signaling pathway in this process. link3 Multipotential neural stem cells (NSCs) and C57BL/6J mice were treated with either gas mixture, isoflurane, or L-theanine 30 min prior to isoflurane exposure, respectively. NSC viability was detected by CCK-8 assay. NSC proliferation and apoptosis were assessed by immunofluorescence and TUNEL assay, respectively. The levels of cleaved caspase-3 and p-Akt and p-GSK-3β in NSCs were tested by Western blotting. Cognitive function of mice was tested by Morris Water Maze at postnatal day (P) 30-35. The results indicated that isoflurane exposure inhibited NSC viability and proliferation, promoted NSC apoptosis as well as increased caspase-3 activation and down-regulated the expressions of p-Akt and p-GSK-3β in NSCs, and that isoflurane exposure on neonatal mice would induce late cognitive impairment. Pretreatment with L-theanine could attenuate isoflurane-caused damage in NSCs and cognitive deficits in young mice. Addinonally, the protective effects of L-theanine on isoflurane-injured NSCs could be reversed by Akt inhibitor Triciribine. Our data showed that pretreatment with L-theanine eliminated the NSC damage and cognitive impairment induced by isoflurane exposure, and that the neuroprotective effect of L-theanine was associated with the Akt/GSK-3β signaling pathway.