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Nucleus pulposus (NP) has been suggested to trigger an autoimmune response if exposed to the immune system, which plays a key role in neuropathic pain. Therefore, appropriate suppression of inflammation is a key factor for treating the radiculopathy caused by intervertebral disk (IVD) degeneration. Resveratrol, a key component of red wine, has been suggested to exhibit anti-inflammatory properties in vitro and in vivo. However, the effects of resveratrol on NP-mediated pain in vivo have not been studied. The aim of the present study was to investigate whether resveratrol may be useful in treating NP-mediated pain in an autologous NP model of radiculopathy. A total of 36 adult male Sprague-Dawley rats were allocated randomly into sham (group I), saline-treated (group II) and resveratrol-treated (group III) groups. Animal behavior in response to non-noxious mechanical stimulation with von Frey filaments was compared at days 0 (baseline), 3, 7, 14 and 21 following surgery. The expression of proinflammatory cytokines such as tumor necrosis factor α (TNF-α) and interleukin-1 (IL-1) were assessed at days 7 and 14. The data showed that resveratrol exhibited an anti-inflammatory effect on the expression of proinflammatory cytokines. Compared with group II, the expression of TNF-α and IL-1 was significantly decreased at each time point in group III. In addition, resveratrol significantly reduced pain behavior triggered by the application of NP tissue on the dorsal root ganglion for up to 14 days. These data suggest that resveratrol has potential for the treatment of NP-mediated pain, indicating a potential clinical application. [ABSTRACT FROM AUTHOR]

The aim of the present study was to assess the neuroprotective effects of tetrahydrocurcumin (THC) in a mouse model of cerebral ischemia/reperfusion (I/R) injury, and to investigate the involvement of Golgi reassembly and stacking protein 65 (GRASP65) and the extracellular signal-regulated kinase (ERK) signaling pathway. Cerebral I/R injury was induced using the Pulsinelli four-vessel occlusion method. After 5 min of reperfusion, mice received THC (5, 10 or 25 mg/kg) or saline by intraperitoneal injection. After 24 h of reperfusion, mice underwent neurological evaluation. Infarct volumes were determined by triphenyltetrazolium chloride staining, and levels of superoxide dismutase and malondialdehyde were measured in brain tissue homogenates. Expression of GRASP65, phosphorylated-GRASP65, ERK and phosphorylated-ERK was determined by western blotting. THC induced a dose-dependent decrease in the phosphorylation of ERK and GRASP65. Thus, THC attenuated I/R injury-induced activation of the ERK signaling pathway and reduced the phosphorylation of GRASP65. THC exhibited a dose-dependent protective effect against cerebral I/R injury, mediated by suppression of the ERK signaling pathway and a subsequent reduction in GRASP65 phosphorylation. The current study provided new information in the research of the cerebral ischemia-reperfusion injury mechanism. [ABSTRACT FROM AUTHOR]

p72 (probable ATP-dependent RNA helicase DDX17) belongs to the DEAD-box RNA helicase family. p72 is important in RNA processing. Thus, the role of p72 in doxorubicin (DOX)-induced cardiomyocyte injury was investigated in the present study. The changes in p72 expression levels were studied in cultured neonatal cardiomyocytes and p72 overexpression was induced using adenovirus vectors. To investigate the production of reactive oxygen species (ROS), dihydroethidium staining was conducted. TUNEL and Hoechst staining were used to indicate cell apoptosis. Microarrays were used to determine the altered expression of microRNAs. In DOX-induced cardiomyocyte injury, the protein expression level of p72 was reduced. Overexpression of p72 protected cardiomyocytes from DOX-induced ROS production and cell apoptosis. p72 reduced the activation of estrogen receptor α (ERα), thereby reducing DOX-induced cell apoptosis. The present study indicated that p72 exerts a protective effect against DOX-induced cell apoptosis via inhibition of ERα activation, indicating this may be a potential target of therapy for cardiac injury. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate whether the mammalian target of rapamycin (mTOR) signaling pathway is activated in invasive breast cancer. The expression levels of phosphorylated (p)-mTOR at ser2448 were detected, as well as the expression levels of its downstream signaling molecules: Eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and p70 ribosomal protein S6 kinase 1 (S6K1). The correlation between p-mTOR, p-4E-BP1, p-S6K1, and the clinicopathological parameters of breast cancer were also determined. p-mTOR, p-4E-BP1 and p-S6K1 expression was detected in 285 breast cancer tumor samples and adjacent normal tissue samples using immunohistochemistry. The expression levels and the location of the proteins were analyzed and compared in the various tissue samples. Multivariate Cox regression was used to analyze the clinicopathological factors and prognosis associated with the tissue samples. The disease-free survival rate was examined using survival analyses and Log-rank tests. The results of the present study indicated that the expression levels of p-mTOR, p-4E-BP1, and p-S6K1 were significantly higher in breast cancer tissue, as compared with normal tissue (P<0.01). p-mTOR was predominantly expressed in the cytoplasm, whereas p-4E-BP1 and p-S6K1 were predominantly co-expressed in the cytoplasm and the nucleus. In addition, p-4E-BP1 and p-S6K1 were more likely to be expressed in the cytoplasm in breast cancer tissue samples, as compared with normal tissue samples (P<0.001). Positive p-mTOR was not significantly correlated with positive p-4E-BP1 and p-S6K1 expression. The survival analyses of the patients with positive p-mTOR, p-4E-BP1, and p-S6K1 tissue samples were not significantly different from those of the patients with negative tissue samples (P>0.05). Thus suggesting that these markers are not adequate risk factors for disease free survival (P>0.05). In conclusion, the results of the present study suggested that p-mTOR, p-4E-BP1, and p-S6K1 are activated in invasive breast cancer. In addition, the exclusive expression of p-4E-BP1 and p-S6K1 in the cytoplasm may be characteristic of progressive breast cancer. However, p-mTOR, p-4E-BP1, and p-S6K1 are not prognostic factors for breast cancer. [ABSTRACT FROM AUTHOR]

The host response to spinal cord injury (SCI) can lead to an ischemic environment that can induce cell death. Therapeutic interventions using neurotrophic factors have focused on the prevention of such reactions in order to reduce this cell death. Vascular endothelial growth factor (VEGF) is a potent angiogenic and vascular permeability factor. We hypothesized in this study that batroxobin would exhibit protective effects following SCI by promoting the expression of VEGF to reduce the levels of apoptosis in a rat model of SCI. Ninety adult female Sprague Dawley rats were divided randomly into sham injury (group I), SCI (group II) and batroxobin treatment (group III) groups. The Basso-Bettie-Bresnahan (BBB) scores, number of apoptotic cells and expression of VEGF were assessed at 1, 3, 5, 7, 14 and 28 days post-injury. The BBB scores were significantly improved in group III compared with those in group II between days 5 and 28 post-injury (P<0.05). At each time-point subsequent to the injury, the number of apoptotic cells in group III was reduced compared with that in group II. Compared with group II, treatment with batroxobin significantly increased the expression of VEGF from day 3 until 2 weeks post-SCI (P<0.05), while no significant difference was observed at day 28. These data suggest that batroxobin has multiple beneficial effects on SCI, indicating a potential clinical application. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effect of U0126 on the formation of glial scars following spinal cord injury (SCI) in a rat model. Ninety adult female Sprague-Dawley rats were divided randomly into sham injury (group I), SCI (group II) and U0126 treatment group III) groups, and functional outcome was observed during the 4 weeks following the injury. The P1 and N1 latencies and P1-N1 amplitudes of somatosensory-evoked potentials (SEPs) were collected one day prior to surgery, on the day of surgery and 14 and 28 days postoperatively. The expression levels of glial fibrillary acidic protein (GFAP) and vimentin (Vim) were assessed 14 and 28 days post-injury. Treatment with U0126 significantly increased locomotor function from the second week until 4 weeks post-SCI. At 14 and 28 days subsequent to the injury, the number of cells that were positive for GFAP expression in the U0126-treated group was significantly reduced and the GFAP-positive cells were observed to be smaller, with a reduced prominence and pale staining. Moreover, the area of glial scarring was smaller compared with that of the SCI controls. Inhibitors of MEK may reduce glial scar formation by suppressing the proliferation of astrocytes, and may improve hindlimb motor function. [ABSTRACT FROM AUTHOR]

As a non-invasive method, positron emission tomography (PET)/computed tomography (CT) using 2-deox y-2-fluoro-18-fluoro-D-glucose (18F-FDG) is applied as a useful modality in the diagnosis of breast cancer. By evaluating glucose metabolism, this method can also be used in staging, restaging and post-therapeutic response evaluation. To evaluate the reliability of the 18F-FDG PET/CT-based peri-tumoral halo uptake layer (PHL) method for assessing tumor size, a total of 79 female patients with breast cancer who underwent 18F-FDG PET/CT, breast ultrasound and magnetic resonance imaging (MRI) evaluations were included in the present study. Upon examination by two independent nuclear medicine radiologists, tumor sizes were estimated by 18F-FDG PET/CT using margins defined as the inner line of the PHL. Pathological tumor sizes were evaluated on the direction of largest diameter indicated by previous imaging examination, which were also utilized as final standards. Statistical analysis of the results suggested that 18F-FDG PET/CT had a more linear correlation with pathology compared with breast ultrasound (r2=0.89 vs. 0.73) and MRI (r2=0.89 vs. 0.69) in terms of tumor size estimation, including a significantly lower bias in size difference relative to pathology. 18F-FDG PET/CT also exhibited improved performance compared with breast ultrasound and MRI in T stage assessment. These results indicated that the 18F-FDG PET/CT-based PHL method was superior to breast ultrasound and MRI, and that it provides sufficient reliability and high accuracy for measuring tumor size in patients with breast cancer. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction, regarded as a key step in the pathophysiological course of diabetic vascular complications, is initiated and deteriorated by advanced glycation end products (AGEs). DL-3-n-butylphthalide (DL-NBP) has been proven to have protective effects on neurons and vascular endothelial cells against ischemic and anoxic damage. The aim of the present study was to investigate whether NBP is able to attenuate AGE-induced endothelial dysfunction in vitro, and also elucidate the possible underlying mechanism. An injury model of human umbilical vein endothelial cells (HUVECs) induced by AGEs (200 μg/ml) was established. The results demonstrated that pretreatment with NBP (1-100 μM) significantly increased HUVEC viability and inhibited the apoptosis induced by AGEs. In addition, AGEs stimulated the expression levels of the receptor for AGEs protein and the downstream protein nuclear factor-κB in HUVECs, which were inhibited by pretreatment with NBP. Furthermore, it significantly reduced reactive oxygen species generation and the level of the inflammatory cytokines, intercellular cell adhesion molecule-1 and monocyte chemotactic protein-1, in HUVECs mediated by AGEs. The current findings indicated that NBP attenuated AGE-induced endothelial dysfunction by ameliorating inflammation and oxidative stress responses. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the expression of vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1 (HIF-1), and to investigate the role of the HIF-1/VEGF signaling pathway following spinal cord injury (SCI). A total of 90 12-week-old Sprague Dawley rats were randomly divided into the following three groups: Sham group (operation without SCI); control group (SCI without ML228 treatment); and treatment group (SCI receiving ML228 treatment). ML228 was administered as it is an activator of HIF-1α. The control and treatment groups were subjected to spinal cord hemisection and motor activity was evaluated using the Basso, Beattie and Bresnahan (BBB) scoring system. Expression of HIF-1α and VEGF in each injured spinal cord section was assessed using immunohistochemistry. Prior to SCI, there were no significant differences in the BBB score among the three groups (P>0.05). However, one day after the operation, the BBB score of the sham group was significantly higher than that of the other two groups (P<0.05) and the BBB scores of the control and treatment groups did not differ significantly (P>0.05). BBB scores 3 and 7 days following surgery were significantly higher in the sham group than the other two groups (P<0.05) and the BBB scores of the treatment group were significantly higher than those of the control group (P<0.05). The expression of HIF-1α and VEGF proteins in all groups were measured 1, 3 and 7 days after the operation, and it was observed that their expression was higher in the treatment group than in the control group (P<0.05). Therefore, the results of the current study suggest that ML228 may effectively activate the HIF-1α/VEGF signaling pathway to promote the expression of HIF-1α and VEGF proteins within the injured segment of the spinal cord, which promotes neural functional recovery following SCI in rats. Therefore, treatment with ML228 may be developed as a novel therapeutic strategy to treat SCI. [ABSTRACT FROM AUTHOR]

The antitumor properties of bacteria have been demonstrated over the past decades. However, the efficacy is limited and unclear. Furthermore, systemic infection remains a serious concern in bacteria treatment. In this study, the effect of YB1, a rationally designed 'obligate' anaerobic Salmonella typhimurium strain, on liver tumor growth and metastasis in a nude mouse orthotopic liver tumor model was investigated. The orthotopic liver tumor model was established in nude mice using the hepatocellular carcinoma cell line MHCC-97L. Two weeks after orthotopic liver tumor implantation, YB1, SL7207 and saline were respectively administered through the tail vein of the mice. Longitudinal monitoring of tumor growth and metastasis was performed using Xenogen IVIS, and direct measurements of tumor volume were taken 3 weeks after treatment. In vitro, MHCC-97L and PLC cells were incubated with YB1 or SL7207 under anaerobic conditions. YB1 was observed to invade tumor cells and induce tumor cell apoptosis and death. The results revealed that all mice in the YB1 group were alive 3 weeks after YB1 injection while all mice in the SL7207 group died within 11 days of the SL7207 injection. The body weight decreased by ~9% on day 1 after YB1 injection and but subsequently recovered. Liver tumor growth and metastases were significantly inhibited following YB1 treatment. By contrast to the control group, a large number of Gr1-positive cells were detected on days 1 to 21 following YB1 treatment. Furthermore, YB1 also effectively invaded tumor cells and induced tumor cell apoptosis and death. In conclusion, YB1 suppressed liver tumor growth and metastasis in a nude mice liver tumor model. The potential mechanism may be through enhancing innate immune response and inducing tumor cell apoptosis and cell death. [ABSTRACT FROM AUTHOR]