Abstract Docosahexaenoic acid (DHA) is verified to have neuroprotective effects on traumatic brain injury (TBI) rats by activating Nrf2 signaling pathway, but the role of NOX 2 in this effect has not been illuminated. So this study explored the role of NOX 2 in TBI models treated with DHA, aiming to complete the mechanism of DHA. TBI rat models were constructed with or without DHA treatment, and H 2 O 2 -induced hippocampal neurons were pretreated with DHA alone or in combination with Nrf2 inhibitor brusatol. The neurological function, cognitive ability, and cerebral edema degree of rats were assessed. The apoptosis rate and viability of cells was measured. The generation of NOX 2 , Nrf2, HO-1 and NQO-1 expression levels, and ROS content in hippocampal CA1 region and hippocampal neurons were detected. DHA could not only improve the neurological function, brain edema and cognitive ability in TBI rats, but also decrease effectively the contents of NOX 2 and ROS in hippocampal CA1 region and hippocampal neurons. DHA promoted the nuclear transposition of Nrf2 and the expression levels of HO-1 and NQO-1 in hippocampal CA1 region and hippocampal neurons. On the contrary, Nrf2 inhibitor brusatol inhibited the nuclear transposition of Nrf2 and the expression levels of HO-1 and NQO-1 in hippocampal neurons, promoted the generation of ROS and NOX 2 , and accelerated cell apoptosis. Both in vivo and in vitro experiments demonstrated that DHA treated TBI by reducing NOX 2 generation that might function on Nrf2 signaling pathway, providing a potential evidence for its clinical application.
Objective:To explore the features of MRI in TCS, and study the relationship between the diagnostic value of MRI and clinical symptoms. Methods:MRI appearance,clinical features and surgical finding from 21 cases of TCS which proved by surgery and pathology were analyzed retrospectively.Results:All patients including intradural lipoma(n=8),diastematomyelia(n=2), double stem spinal cord(n=1),teratoma(n=3),cyst(n=1),myelomeningocele(n=6).All cases were spinal dysraphism,6 cases were asymptomatic and diagnosis of TCS was made by regular examination.MRI features were consistent with the findings in operation and symptom.Conclusion:MRI examination is of important value in the diagnosis of TCS,which can nicely reveal the position and the shape of spinal cord conus.MRI can also show the TCS associated malformation and provide the dependable basis for surgical operation.
Cancer patients frequently develop chemotherapy-induced peripheral neuropathy (CIPN), a painful and long-lasting disorder with profound somatosensory deficits. There are no effective therapies to prevent or treat this disorder. Pathologically, CIPN is characterized by a “dying-back” axonopathy that begins at intra-epidermal nerve terminals of sensory neurons and progresses in a retrograde fashion. Calcium dysregulation constitutes a critical event in CIPN, but it is not known how chemotherapies such as paclitaxel alter intra-axonal calcium and cause degeneration. Here, we demonstrate that paclitaxel triggers Sarm1-dependent cADPR production in distal axons, promoting intra-axonal calcium flux from both intracellular and extracellular calcium stores. Genetic or pharmacologic antagonists of cADPR signaling prevent paclitaxel-induced axon degeneration and allodynia symptoms, without mitigating the anti-neoplastic efficacy of paclitaxel. Our data demonstrate that cADPR is a calcium modulating factor that promotes paclitaxel-induced axon degeneration and suggest that targeting cADPR signaling provides a potential therapeutic approach for treating CIPN.
Introduction: Genome-wide association studies have identified ADAMTS7 (a disintegrin and metalloproteinase with thrombospondin motifs, member 7) as risk locus for coronary artery disease (CAD). Sub...
The key step of the protonmotive Q-cycle mechanism of the cytochrome bc(1) complex is the bifurcated oxidation of ubiquinol at the Qp site. It was postulated that the iron-sulfur protein (ISP) accepts the first electron from ubiquinol to generate ubisemiquinone anion to reduce b(L). Because of the difficulty of following the reduction of ISP optically, direct evidence for the early involvement of ISP in ubiquinol oxidation is not available. Using the ultra-fast microfluidic mixer and the freeze-quenching device, coupled with EPR, we have been able to determine the presteady-state kinetics of ISP and cytochrome b(L) reduction by ubiquinol. The first-phase reduction of ISP starts as early as 100 micros with a t(1/2) of 250 micros. A similar reduction kinetic is also observed for cytochrome b(L), indicating a simultaneous reduction of both ISP and b(L). These results are consistent with the fact that no ubisemiquinone was detected at the Qp site during oxidation of ubiquinol. Under the same conditions, by using stopped flow, the reduction rates of cytochromes b(H) and c(1) were 403 s(-1) (t(1/2) 1.7 ms) and 164 s(-1) (t(1/2) 4.2 ms), respectively.
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