Reactive oxygen species (RoS) are involved in the development of pains in various conditions, including neuropathic and inflammatory pain [1][2][3][4][5] . Park et al reported increased RoS in the spinal cord of rats after peripheral nerve injury 6 . others found that treatment with RoS scavengers phenyl Ntert-butylnitrone (PbN), 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (tEMPoL), 5,5-dimethylpyrroline -N-oxide (DMPo) or vitamin E could temporarily reverse the allodynia developed after nerve ligation in rats 2,7,8 . the function mechanisms of RoS scavenger, like that of PbN-induced analgesic effect, are reported to be mediated mainly via spinal mechanisms 2 .ABSTRACT: Background: Reactive oxygen species (RoS) are often associated with persistent pains such as neuropathic and inflammatory pain. Hydrogen gas can reduce RoS and alleviate cerebral, myocardial, and hepatic ischemia/reperfusion injuries. in the present study, we aim to investigate whether hydrogen-rich saline can reduce neuropathic pain in a rat model of chronic constriction injury (CCi). Methods: thirty SD rats were randomly divided into three groups: sham group was administered sodium chloride by intrathecal injection (n=10); control groups underwent CCi surgery and were administered sodium chloride by intrathecal injection (n=10); vehicle group underwent CCi surgery and was administered hydrogen-rich saline by intrathecal injection (n=10). Drugs were administered in the dose of 100ul/kg once a day at 0.5 hours before and 1-7 day after CCi surgery. the mechanical thresholds were tested at one day before and 3-14 day after CCi surgery. Results: We found that hydrogen-rich saline significantly elevated the mechanical thresholds of neuropathic pain compared to vehicle (physiologic saline) control in CCi rats (p<0.05); it also decreased the levels of myeloperoxidase, maleic dialdehyde, and protein carbonyl in spinal cord by 7 days post-chronic constriction injury(p<0.05). in addition, hydrogen-rich saline also suppressed the expression of p38-mitogen-activated protein kinase (p38MAPK) and brain-derived neurotrophic factor (bDNF) in the spinal cord by 7 days post-chronic constriction injury (p<0.01, p<0.01, respectively), but had no effect on P2X4R (p>0.05), an AtP receptor. Conclusion: intrathecal injection of hydrogen-rich saline can decrease oxidative stress and the expression of p38MAPK and bDNF that may contribute to the elevated threshold of neuropathic pain in rat CCi model. RÉSUMÉ:Le salin riche en hydrogène atténue la douleur névropathique en réduisant le stress oxydatif. Contexte : Les espèces réactives oxygénées (RoS) sont souvent associées à la douleur persistante comme la douleur névropathique et la douleur inflammatoire. Le gaz hydrogène peut réduire les RoS et soulager le dommage dû à l'ischémie/la reperfusion au niveau cérébral, myocardique et hépatique. Le but de cette étude était de déterminer si le salin riche en hydrogène peut réduire la douleur névropathique chez un modèle de lésion par constriction chronique (LCC) chez le rat. ...
Hepatocellular carcinoma (HCC) is a hyper-vascular malignancy and mostly accompany with chronic hepatitis and liver cirrhosis, which usually exist intra and extra-hepatic metastasis such as portal vein tumor emboli [1, 2] . HCC treatment options are severely limited by the frequent presence of relapse after surgery and poor prognosis. Angiogenesis is prerequisite for HCC occurrence and development, and regulated by hypoxia inducible factor-1α (HIF-1α) expression [3] .HIF-1α is a key transcription factor, which mediates physiological and pathological hypoxia response. Under hypoxic conditions, HIF-1α over-expresses and activates expressions of many hypoxia-response genes, leading to closely associate with HCC ecosystem for tumor growth, infiltration, metastasis, prognosis and treatment resistance in HCC. In the present study, we briefly showed the expression of hepatic HIF-1α in patients with liver disease and established a functional inactivation of HIF-1α in HepG2 cells via miRNA to determine HIF-1α's role for anti-angiogenesis and investigated the effects of HIF-1α miRNA on cell cycle and apoptosis with or without synergization with doxorubicin. Materials and methods Liver cancer specimensAccording to self-control method, the HCC and surrounding tissues were collected from 35 HCC patients undergoing curative hepatectomy at the Affiliated Hospital of Nantong University, China, during the period Abstract Objective: The aim of this study was to analyze the expression features of hypoxia inducible factor-1α (HIF-1α) in hepatocellular carcinoma (HCC) and effects of HIF-1α silencing on HepG2 cells. Methods: HIF-1α expression was analyzed in the self-control HCC specimens by immunohistochemistry. After HepG2 cells with miRNA transfection, the expression of HIF-1α was determined at mRNA or protein level by real-time polymerase chain reaction (PCR) or Western blotting. Vascular endothelial growth factor (VEGF) and angiopoietin-2 (ANG-2) were determined by ELISA. Alterations of cell cycles and apoptosis of HepG2 cells were measured using a flow cytometer. Results: Positive HIF-1α was brown and granule-like in the cytoplasm or nucleus. Significant difference was found between HCC (80%) and its surrounding tissues (100%, χ 2 = 22.35, P < 0.001) and HIF-1α expression related to tumor size. At 72 h after miRNA transfection, the expression of HIF-1α in HepG2 cells was down-regulated by 87% at mRNA or 65% at protein level, with VEGF and ANG-2 decreased to 54% and 36%, respectively. After RNA interference combined with anti-cancer drug, the apoptotic rate of HepG2 cells was increasing from 22.46% ± 0.61% to 36.99% ± 0.88%, with up-regulation of G1 phase (65.68% ± 0.91%) and down-regulation of S phase (19.47 ± 1.34 %). Conclusion: Abnormal expression of HIF-1α is associated with development of HCC, and HIF-1α gene silencing can effectively inhibit HepG2 cell proliferation.
Propofol inhibits long-term potentiation (LTP) in the hippocampal CA1 region and impedes episodic memory formation. However, the molecular mechanisms involved in the effect of propofol are still poorly understood. It had been reported that propofol inhibited cAMP response element binding protein signaling, which was proposed to contribute to memory retention impairment in rats. Here, we first demonstrated that propofol perfusion could inhibit forskolin induced LTP in the rat hippocampal CA1 slices. Propofol also reduced the level of cAMP, which could be reversed by non-selective PDE inhibitor IBMX. We further discovered that propofol could increase both PDE4 activity and PDE4AX protein expressions in the hippocampal CA1 region. Furthermore, pretreatment of rolipram, a PDE4 inhibitor, rescued propofol induced inhibition of CA1 LTP and the impairment of hippocampus-dependent memory formation in rats. Thus, our results suggest that reduced levels of cAMP by increasing PDE4 activity and PDE4AX protein expressions in the hippocampal CA1 region plays an important role in the propofol-induced amnesia.
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