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Berlin Brandenburg

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  • 1
    Language: English
    In: Pharmacology, biochemistry, and behavior, November 2013, Vol.112, pp.56-63
    Description: NR2B subunits (NMDA receptor 2B subunit) play an important role in generation of pain and forming central sensitization of pain. Ro 25-6981, a highly selective NR2B antagonist, gained much attention in recent years. In this study, we used a rat model of incisional pain to investigate effects of postoperative analgesia and changes of postoperative hyperalgesia induced by remifentanil through the pretreatment of intrathecal administration with Ro 25-6981. The behavioral changes of rats have been evaluated by the paw withdrawal mechanical threshold and paw withdrawal thermal latency after intrathecal injection of Ro 25-6981. The expression of NR2B with tyrosine phosphorylation in the spinal dorsal horn was analyzed by Western blotting. Intrathecal injection of Ro 25-6981 significantly enhanced the paw withdrawal mechanical threshold and paw withdrawal thermal latency after the operation. Significant change has been observed after intrathecal injection of 800.0 μg of Ro 25-6981 and at 2h after operation in the oblique pull test degree and BBB rating score. Pretreatment of Ro 25-6981 decreased the high level expression of NR2B with tyrosine phosphorylation in spinal dorsal horn of the rat model after the operation. Intrathecal injection of Ro 25-6981 had significant analgesic effects on incision pain in rats and effectively attenuated postoperative hyperalgesia induced by remifentanil.
    Keywords: Antinociception ; Hyperalgesia ; Intrathecal Administration ; N-Methyl-D-Aspartate Receptor ; Prevention ; Ro 25-6981 ; Analgesics -- Pharmacology ; Hyperalgesia -- Prevention & Control ; Phenols -- Pharmacology ; Piperidines -- Pharmacology ; Receptors, N-Methyl-D-Aspartate -- Antagonists & Inhibitors
    ISSN: 00913057
    E-ISSN: 1873-5177
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  • 2
    Language: English
    In: Pharmacology, Biochemistry and Behavior, 2015, Vol.134, p.35(7)
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.pbb.2015.04.015 Byline: Ming Jiang, Wei Zhang, Chongxue Cheng, Zhengliang Ma, Xiaoping Gu Abstract: Remifentanil is a short-acting and highly selective mu opiate agonist that is used in many clinical surgical situations for intraoperative pain relief. Under certain conditions, remifentanil can produce "paradoxical" hyperalgesia. This study aims to investigate mechanisms of actions mediating this "paradoxical" effect. Article History: Received 16 October 2014; Revised 8 April 2015; Accepted 17 April 2015
    ISSN: 0091-3057
    Source: Cengage Learning, Inc.
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  • 3
    Language: English
    In: Pharmacology, Biochemistry and Behavior, Nov 1, 2013, Vol.112, p.56(8)
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.pbb.2013.09.007 Byline: Ming Jiang, Wei Zhang, Zhengliang Ma, Xiaoping Gu Abstract: NR2B subunits (NMDA receptor 2B subunit) play an important role in generation of pain and forming central sensitization of pain. Ro 25-6981, a highly selective NR2B antagonist, gained much attention in recent years. In this study, we used a rat model of incisional pain to investigate effects of postoperative analgesia and changes of postoperative hyperalgesia induced by remifentanil through the pretreatment of intrathecal administration with Ro 25-6981. Article History: Received 26 March 2013; Revised 8 August 2013; Accepted 18 September 2013
    Keywords: Aspartate -- Analysis ; N-methyl-d-aspartate -- Analysis
    ISSN: 0091-3057
    Source: Cengage Learning, Inc.
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  • 4
    Language: English
    In: Biomaterials, September 2013, Vol.34(28), pp.6717-6728
    Description: With the increasing application of microRNAs (miRNAs) in the treatment and monitoring of different diseases, miRNAs have become an important tool in biological and medical research. Recent studies have proven that miRNAs are involved in the osteogenic differentiation of stem cells. However, few studies have reported the use of miRNA-modified adult stem cells to repair critical-sized defects (CSDs) using tissue engineering technology. It is known that miR-31 is a pleiotropically acting miRNA that inhibits cancer metastasis and targets special AT-rich sequence-binding protein 2 (Satb2) in fibroblasts. However, it is not clear whether the function of miR-31 is to enhance adipose tissue-derived stem cell (ASC) osteogenesis, along with its association with Satb2, during osteogenic differentiation and bone regeneration. In this study, we systematically evaluated the function of miR-31 in enhancing ASC osteogenesis and the therapeutic potential of miR-31-modified ASCs in a rat CSD model with β-tricalcium phosphate (β-TCP) scaffolds. ASCs were treated with lentivirus (Lenti)-miR-31, Lenti-as-miR-31 (antisense) or Lenti-NC (negative control). These genetically modified ASCs were then combined with β-TCP scaffolds to repair CSDs in rats. The results showed that in cultured ASCs in vitro, Lenti-as-miR-31 significantly enhanced osteogenic mRNA and protein expression when compared with the Lenti-NC group. Moreover, we firstly found that a Runt-related transcription factor 2 (Runx2), Satb2 and miR-31 regulatory loop triggered by bone morphogenetic protein-2 (BMP-2) plays an important role in ASCs' osteogenic differentiation and bone regeneration. More importantly, we found that miR-31-knockdown ASCs dramatically improved the repair of CSDs, including increased bone volume, increased bone mineral density (BMD) and decreased scaffold residue in vivo. These data confirm the essential role of miR-31-modified ASCs in osteogenesis in vitro and in vivo.
    Keywords: Mir-31 ; Ascs ; Osteogenesis ; Csd ; Bone Repair ; Tissue Engineering
    ISSN: 0142-9612
    E-ISSN: 18785905
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  • 5
    Language: English
    In: Cancer Research, 07/01/2017, Vol.77(13 Supplement), pp.1226-1226
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
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  • 6
    Language: English
    In: Pharmacology, Biochemistry and Behavior, 1 November 2013, Vol.112, pp.56-63
    Description: BackgroundNR2B subunits (NMDA receptor 2B subunit) play an important role in generation of pain and forming central sensitization of pain. Ro 25-6981, a highly selective NR2B antagonist, gained much attention in recent years. In this study, we used a rat model of incisional pain to investigate effects of postoperative analgesia and changes of postoperative hyperalgesia induced by remifentanil through the pretreatment of intrathecal administration with Ro 25-6981. MethodsThe behavioral changes of rats have been evaluated by the paw withdrawal mechanical threshold and paw withdrawal thermal latency after intrathecal injection of Ro 25-6981. The expression of NR2B with tyrosine phosphorylation in the spinal dorsal horn was analyzed by Western blotting. ResultsIntrathecal injection of Ro 25-6981 significantly enhanced the paw withdrawal mechanical threshold and paw withdrawal thermal latency after the operation. Significant change has been observed after intrathecal injection of 800.0μg of Ro 25-6981 and at 2h after operation in the oblique pull test degree and BBB rating score. Pretreatment of Ro 25-6981 decreased the high level expression of NR2B with tyrosine phosphorylation in spinal dorsal horn of the rat model after the operation. ConclusionsIntrathecal injection of Ro 25-6981 had significant analgesic effects on incision pain in rats and effectively attenuated postoperative hyperalgesia induced by remifentanil. •Ro 25-6981 is a highly selective NR2B antagonist.•Ro 25-6981 has significant analgesic effects on incision pain in rats.•Ro 25-6981 attenuates postoperative hyperalgesia.
    Keywords: Antinociception ; Prevention ; Hyperalgesia ; Intrathecal Administration ; Ro 25-6981 ; N-Methyl- D -Aspartate Receptor
    ISSN: 0091-3057
    Source: ScienceDirect (Elsevier B.V.)
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  • 7
    Language: English
    In: The Journal of infectious diseases, November 2012, Vol.206(9), pp.1407-14
    Description: Haemophilus ducreyi encounters several classes of antimicrobial peptides (APs) in vivo and utilizes the sensitive-to-antimicrobial-peptides (Sap) transporter as one mechanism of AP resistance. A mutant lacking the periplasmic solute-binding component, SapA, was somewhat more sensitive to the cathelicidin LL-37 than the parent strain and was partially attenuated for virulence. The partial attenuation led us to question whether the transporter is fully abrogated in the sapA mutant. We generated a nonpolar sapBC mutant, which lacks both inner membrane permeases of the Sap transporter, and tested the mutant for virulence in human volunteers. In vitro, we compared LL-37 resistance phenotypes of the sapBC and sapA mutants. Unlike the sapA mutant, the sapBC mutant was fully attenuated for virulence in human volunteers. In vitro, the sapBC mutant exhibited significantly greater sensitivity than the sapA mutant to killing by LL-37. Similar to the sapA mutant, the sapBC mutant did not affect H. ducreyi's resistance to human defensins. Compared with the sapA mutant, the sapBC mutant exhibited greater attenuation in vivo, which directly correlated with increased sensitivity to LL-37 in vitro. These results strongly suggest that the SapBC channel retains activity when SapA is removed.
    Keywords: Drug Resistance, Bacterial ; Antimicrobial Cationic Peptides -- Pharmacology ; Haemophilus Ducreyi -- Enzymology ; Membrane Transport Proteins -- Metabolism ; Virulence Factors -- Metabolism
    ISSN: 00221899
    E-ISSN: 1537-6613
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  • 8
    Language: English
    In: Pharmacology, Biochemistry and Behavior, Sept, 2014, Vol.124, p.19(8)
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.pbb.2014.05.003 Byline: Yue Liu, Ying Liang, Bailing Hou, Ming Liu, Xuli Yang, Chenglong Liu, Juan Zhang, Wei Zhang, Zhengliang Ma, Xiaoping Gu Abstract: The N-methyl-d-aspartate receptor (NMDAR) containing subunit 2B (NR2B) is critical for the regulation of nociception in bone cancer pain, although the precise molecular mechanisms remain unclear. KIF17, a kinesin motor, plays a key role in the dendritic transport of NR2B. The up-regulation of NR2B and KIF17 transcription results from an increase in phosphorylated cAMP-response element-binding protein (CREB), which is activated by calcium/calmodulin-dependent protein kinase II (CaMKII). In this study, we hypothesized that CaMKII-mediated KIF17/NR2B trafficking may contribute to bone cancer pain. Osteosarcoma cells were implanted into the intramedullary space of the right femurs of C3H/HeJ mice to induce progressive bone cancer-related pain behaviors. The expression of spinal t-CaMKII, p-CaMKII, NR2B and KIF17 after inoculation was also evaluated. These results showed that inoculation of osteosarcoma cells induced progressive bone cancer pain and resulted in a significant up-regulation of p-CaMKII, NR2B and KIF17 expression after inoculation. Intrathecal administration of KN93, a CaMKII inhibitor, down-regulated these three proteins and attenuated bone cancer pain in a dose- and time-dependent manner. These findings indicated that CaMKII-mediated KIF17/NR2B trafficking may contribute to bone cancer pain, and inhibition of CaMKII may be a useful alternative or adjunct therapy for relieving cancer pain. Article History: Received 11 September 2013; Revised 31 March 2014; Accepted 8 May 2014
    Keywords: Aspartate ; N-Methyl-D-Aspartate ; Cancer Prevention ; Cancer Pain ; Bone Cancer ; Proteins ; Pain Management ; Protein Binding ; Protein Kinases
    ISSN: 0091-3057
    Source: Cengage Learning, Inc.
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  • 9
    Language: English
    In: 2012, Vol.7(9), p.e45575
    Description: The root of Polygala tenuifolia, a traditional Chinese medicine, has been used to improve memory and intelligence, while the underlying mechanisms remain largely unknown. In this study, we investigated the protective effects of senegenin, an component of Polygala tenuifolia root extracts, on cognitive dysfunction induced by hepatic ischemia-reperfusion. ; Initially, we constructed a rat model of hepatic ischemia-reperfusion (HIR) and found that the memory retention ability of rats in the step-down and Y maze test was impaired after HIR, paralleled by a decrease of N-methyl-D-aspartate (NMDA) receptor NR2B subunit mRNA and protein expressions in hippocampus. Furthermore, we found that administration of senegenin by gavage attenuated HIR-induced cognitive impairment in a dose and time dependent manner, and its mechanisms might partly due to the increasing expression of NR2B in rat hippocampus. ; Cognitive dysfunction induced by HIR is associated with reduction of NR2B expression. Senegenin plays a neuroprotective role in HIR via increasing NR2B expression in rat hippocampus. These findings suggest that senegenin might be a potential agent for prevention and treatment of postoperative cognitive dysfunction (POCD) or other neurodegenerative diseases.
    Keywords: Research Article ; Biology ; Medicine ; Neuroscience ; Pharmacology
    E-ISSN: 1932-6203
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  • 10
    Language: English
    In: PLoS ONE, 2012, Vol.7(6), p.e39897
    Description: Microglia might play an important role in nociceptive processing and hyperalgesia by neuroinflammatory process. Mineralocorticoid receptor (MR) expressed on microglia might play a central role in the modulation of microglia activity. However the roles of microglia and MR in radicular pain were not well understood. This study sought to investigate whether selective MR antagonist spironolactone develop antinociceptive effects on radicular pain by inhibition neuroinflammation induced by spinal microglia activation. ; Radicular pain was produced by chronic compression of the dorsal root ganglia with SURGIFLO™. The expression of microglia, interleukin beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), NR1 subunit of the NMDA receptor (t-NR1), and NR1 subunit phosphorylated at Ser896 (p-NR1) were also markedly up-regulated. Intrathecal injection of spironolactone significantly attenuated pain behaviors as well as the expression of microglia, IL-1β, TNF-α, t-NR1, and p-NR1, whereas the production of IL-6 wasn’t affected. ; These results suggest that intrathecal delivery spironolactone has therapeutic effects on radicular pain in rats. Decreasing the activation of glial cells, the production of proinflammatory cytokines and down-regulating the expression and phosphorylation of NMDA receptors in the spinal dorsal horn and dorsal root ganglia are the main mechanisms contributing to its beneficial effects.
    Keywords: Research Article ; Biology ; Medicine ; Physics ; Physiology ; Pharmacology ; Anesthesiology And Pain Management ; Physics
    E-ISSN: 1932-6203
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