Meadray6255

Glutaredoxin 2 (GRX2) is an antioxidative protein that exerts a key role in various pathological processes. However, whether GRX2 participates in modulating the oxidative stress during cerebral ischemia/reperfusion, injury is undermined. This study aimed to determine the potential role of GRX2 in regulating oxidative stress in cultured neurons induced by oxygen-glucose deprivation/reoxygenation (OGD/R), a cellular model for study of cerebral ischemia/reperfusion injury in vitro. Here, we showed that GRX2 expression was decreased in neurons subjected to OGD/R exposure. The upregulation of GRX2 markedly improved the viability of OGD/R-exposed neurons and caused a marked reduction in OGD/R-induced apoptosis and reactive oxygen species (ROS) production. On the contrary, depletion of GRX2 exacerbated the OGD/R-induced apoptosis and ROS production in cultured neurons. Moreover, GRX2 upregulation increased nuclear expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and enhanced the activation of Nrf2/ARE signaling associated with modulation of glycogen synthase kinase-3β (GSK-3β) inhibition. Notably, inhibition of Nrf2 markedly abrogated GRX2-mediated protection against OGD/R-induced apoptosis and oxidative stress. Overall, these findings elucidate that GRX2 plays an essential role in regulating the protection against OGD/R-induced apoptosis and oxidative stress in neurons associated with its ability to enhance the activation of Nrf2 via modulation of GSK-3β. Our study indicates that GRX2 may play a key role in modulating neuronal apoptosis and oxidative stress induced by cerebral ischemia/reperfusion injury.The potential mechanism of neuroblastoma (NB) progression remains elusive. We intended to uncover the role and network of long noncoding RNA (lncRNA) double homeobox A pseudogene 8 (DUXAP8) in NB. Quantitative real time polymerase chain reaction (qRT-PCR) was performed to detect the levels of DUXAP8, microRNA-29 (miR-29) and nucleolar protein 4 like (NOL4L). The proliferation, colony formation, cell cycle and metastasis of NB cells were examined by (4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, plate colony formation assay, flow cytometry and transwell assays. Western blot was conducted to detect the expression of metastasis and proliferation-associated proteins and NOL4L. Ruboxistaurin order The target relationship was predicted by StarBase software and was confirmed by dual-luciferase reporter assay and RNA binding protein immunoprecipitation (RIP) assay. Nude mice bearing tumors were used to verify the role of DUXAP8 in vivo. We found the expression of DUXAP8 was positively related to the stage of NB tumors, and it was negatively associated with the survival rate of NB patients. DUXAP8 knockdown inhibited the proliferation, colony formation, cycle and motility of NB cells. MiR-29 could interact with DUXAP8, and DUXAP8 exacerbated NB via sponging miR-29. MiR-29 could bind to NOL4L, and the influence of NOL4L intervention on the functions of NB cells could be alleviated by the transfection of miR-29 inhibitor. NOL4L was regulated by DUXAP8/miR-29 axis in NB cells. DUXAP8 knockdown blocked the progression of NB in vivo. Collectively, DUXAP8 deteriorated NB through serving as a sponge for miR-29 to up-regulate the expression of NOL4L in vitro and in vivo.The α2-adrenergic receptor (α2-AR) agonist dexmedetomidine increases baroreflex sensitivity (BRS). In the current study, we examined the potential role of adenosine A1 receptor (A1R) within the nucleus tractus solitaries (NTS) in such a response. Briefly, adult male Sprague-Dawley rats were anesthetized and randomly received microinjection of selective A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 0.1 pmol/1 μl) or saline vehicle into the right NTS. Ten min after the microinjection, dexmedetomidine infusion started at a rate of 30 μg/kg over 15 min followed by infusion at 15 μg·kg-1·h-1 for 105 min, or 100 μg/kg over 15 min followed by infusion at 50 μg·kg-1·h-1 for 105 min. BRS was examined using a standard phenylephrine method prior to infusion (T0), 60 min (T1) and 120 min (T2) after dexmedetomidine infusion started. Adenosine concentration in plasma and brainstem was measured with high-performance liquid chromatography with vs. without α2-AR antagonist atipamezole pretreatment (0.5 mg/kg, i.p.). Dexmedetomidine increased BRS at both 30 (T0 0.55 ± 0.25 vs. T1 2.45 ± 0.37, T2 2.26 ± 0.56 ms/mmHg, P less then 0.05) and 100 μg/kg (T0 0.63 ± 0.24 vs. T1 6.21 ± 1.87, T2 6.30 ± 2.12 ms/mmHg, P less then 0.05). DPCPX pretreatment obliterated BRS response to 100-μg/kg dexmedetomidine. At 100 μg/kg, dexmedetomidine increased adenosine concentration in plasma (0.23 ± 0.11 to 0.45 ± 0.07 μg/ml, P less then 0.05) and brainstem (1.46 ± 0.30 to 2.52 ± 0.22 μg/ml, P less then 0.05); such effect was blocked by atipamezole pretreatment. Western blot analysis showed α2-AR up-regulation by 100-μg/kg dexmedetomidine, which can be prevented by DPCPX. Double-labeling with glial fibrillary acidic protein showed α2-AR up-regulation in astrocytes in the NTS. These results suggest that dexmedetomidine enhances baroreflex sensitivity, possibly by increasing adenosine in NTS and α2-AR expression in astrocytes.The timing of organisms' senescence is developmentally programmed but also shaped by the interaction between environmental inputs and life-history traits. In ectotherms, ageing dynamics are still poorly understood even though their body temperature, metabolism, or growth trajectory are very sensitive to environmental changes. Here, we investigated the role of life-history traits such as age, sex, body size, body condition, and tail autotomy (i.e self-amputation) in shaping telomere length in six populations of the Algerian sand lizard (Psammodromus algirus) distributed along an elevational gradient from 300 to 2500 m above the sea level. Additionally, we compiled the available information on reptiles' telomere length in a review table. Our cross-sectional study shows that older lizards have longer telomeres, which might be mostly linked to the selective disappearance of individuals with shorter telomeres or, alternatively, mediated by a higher expression of telomerase across their life. In fact, variation in telomere length across elevation was explained by age structure of lizards; thus, in contrast to our predictions, altitude had no effect on telomere length in this study system.