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Yan H.,Daping Hospital | Xu F.-L.,Daping Hospital | Xu F.-L.,Third Military Medical University | Wu X.-H.,State Key Laboratory of Trauma | And 12 more authors.
Journal of Immunotherapy | Year: 2013

Many studies have suggested that the synergic effect of myeloid differential protein-2 (MD-2) on bacterial lipopolysaccharide (LPS) stimulation of toll-like receptor 4 (TLR4) may be a critical step during the LPS-TLR4 response signaling pathway. We performed a bioinformatic analysis on the MD-2 protein and identified the amino acid sequence NH2-FSKGKYKCV-COOH (K128-132) as a possible key sequence involved in the binding between MD-2 and LPS. We then screened a random phage display peptide library using this sequence as bait in order to identify antagonistic peptides. After 3 rounds of selection, 3 positive clones were identified. All 3 peptides were shown to inhibit, in a dose-dependent manner the production of tumor necrosis factor-α and interleukin-6 in human U937 and THP-1 cell lines as well as human peripheral blood monocytes stimulated by LPS. Only 2 of the 3 peptides were able to bind MD-2 directly as shown by sulfo-SBED biotin label transfer experiments. BALB/C mice were used to estimate the protection of these peptides from LPS challenge, and 2 of the 3 peptides (Lys-Thr-Val-Pro-Asp-Asn-His and Ile-Gly-Lys-Phe-Leu- Tyr-Arg) reduced mortality of the challenged mice from 100% to 53.8%. This study has demonstrated that interfering with the binding between MD-2 and LPS might be a potential therapeutic strategy for treating LPS-induced sepsis, and in doing so has identified 2 potential peptide candidates. Copyright © 2013 by Lippincott Williams & Wilkins.

Li B.C.,Third Military Medical UniversityChongqing | Li B.C.,State Key Laboratory of Trauma | Li Y.,451 Hospital | Xu C.,Third Military Medical UniversityChongqing | And 12 more authors.
Neurological Research | Year: 2014

Objective: To study blast-induced traumatic brain injury (bTBI) characteristics in confined space.Methods: The goats were placed at the column-like buildings with trinitrotoluene (TNT) as the source of the blast wave. The pressure was recorded at 2-8 m from the explosion center. The systemic physiology, electroencephalogram (EEG), serum level of S-100beta, and neuron specific enolase (NSE) were determined pre and post the exposure. Neuroanatomy and neuropathology were observed 4 hours after the exposure.Results: The blast waveform was composed of two peaks from the incident and reflection wave with a range of pressure-duration from 555/913 kPa-0.663 milliseconds at 2 m to 45/71 kPa-2.7/2.367 milliseconds at 8 m. At 2 m, the goats experienced brain depression while the heart rate and respiratory rate concomitantly increased with bloody foam fluid emission from the nose and the mouth. Of the goats, 88.89% were burned. The distinctive gross neuroanatomical changes were congestive expansion of surface vessels on the hemisphere cerebellum and brainstem along with subarachnoid hemorrhage on the frontal lobe, mesencephalon, and brainstem. Subarachnoid hemorrhage, enlarged perivascular space, vascular dilatation and congestion, and parenchymal hemorrhagic could be easily observed microscopically. High amplitude and low frequency of waveforms appeared in the EEG. The serum concentration of S-100beta and NSE were elevated. Although these pathophysiological changes diminished with increasing distance from the explosive center, these changes existed for the 8 m subjects.Conclusions: Blast-induced traumatic brain injury can be induced by a complex blast wave with a pressure and duration of 45/71 kPa and 2.7/2.367 milliseconds. Its severity is related to the features and waveforms of the blast. © W. S. Maney & Son Ltd 2014.

Chen H.-J.,Chongqing Medical University | Chen H.-J.,State Key Laboratory of Trauma | Xu C.,Chongqing Medical University | Xu C.,State Key Laboratory of Trauma | And 15 more authors.
Chinese Journal of Traumatology - English Edition | Year: 2015

Purpose We once reported blast-induced traumatic brain injury (bTBI) in confined space. Here, bTBI was studied again on goats in the open air using 3.0 kg trinitrotoluene. Methods The goats were placed at 2, 4, 6 and 8 m far from explosion center. Trinitrotoluene (TNT) was used as the source of the blast wave and the pressure at each distance was recorded. The systemic physiology, electroencephalogram, serum level of S-100beta, and neuron specific enolase (NSE) were determined pre and post the exposure. Neuroanatomy and neuropathology were observed 4 h after the exposure. Results Simple blast waveforms were recorded with parameters of 702.8 kPa-0.442 ms, 148.4 kPa-2.503 ms, 73.9 kPa-3.233 ms, and 41.9 kPa-5.898 ms at 2, 4, 6 and 8 m respectively. Encephalic blast overpressure was on the first time recorded in the literature by us at 104.2 kPa-0.60 ms at 2 m, where mortality and burn rate were 44% and 44%. Gross examination showed that bTBI was mainly manifested as congestive expansion of blood vessels and subarachnoid hemorrhage, which had a total incidence of 25% and 19% in 36 goats. Microscopical observation found that the main pathohistological changes were enlarged perivascular space (21/36, 58%), small hemorrhages (9/36, 25%), vascular dilatation and congestion (8/36, 22%), and less subarachnoid hemorrhage (2/36, 6%). After explosion, serum levels of S-100β and NSE were elevated, and EEG changed into slow frequency with declined amplitude. The results indicated that severity and incidence of bTBI is related to the intensity of blast overpressure. Conclusion Blast wave can pass through the skull to directly injure brain tissue. © 2015 Production and hosting by Elsevier B.V.

Zhang J.,Chongqing Medical University | Zhang J.,State Key Laboratory of Trauma | Liu Z.,Chongqing Medical University | Liu Z.,State Key Laboratory of Trauma | And 10 more authors.
Journal of Molecular Neuroscience | Year: 2014

Cell-based therapy is a promising strategy for the repair of spinal cord injury (SCI), and the synergic effects of donor cells are emphasized in recent years. In this study, epidermal neural crest stem cells (EPI-NCSCs) and olfactory ensheathing cells (OECs) were transplanted into the contused spinal cord of rats separately or jointly at 1 week after injury. At 3 and 9 weeks posttransplantation, migration of the donor cells, expression of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) and functional recovery of the contused cord were determined by techniques of histopathology, quantitative real-time polymerase chain reaction (qPCR), immunohistochemistry and Basso–Beattie–Bresnahan (BBB) score. The results showed that the migration and distribution of EPI-NCSCs in vivo were promoted by OECs at 3 weeks after transplantation, but they vanished at 9 weeks. The expression of BDNF and GDNF was significantly increased by co-transplantation at molecular and protein level. Although the expression of both factors in EPI-NCSCs- and OECs-injected group was lower than in co-injected group, it was higher than in control groups. Similarly, the best locomotor recovery of the contused cord was acquired from co-injected animals. As we know, this is the first time to study the synergic effects of EPI-NCSCs and OECs, and the data indicates that donor cells migration, expression of neurotrophic factors (NTFs), and recovery of motor function can be improved by EPI-NCSCs and OECs synergistically. © 2014, Springer Science+Business Media New York.

Xu C.,Chongqing Medical University | Xu C.,State Key Laboratory of Trauma | Chen Y.,Chongqing Medical University | Chen Y.,State Key Laboratory of Trauma | And 12 more authors.
Technology and Health Care | Year: 2015

To establish a finite element (FE) model of the pig head for simulating firearm wounds. An experimental study was carried out by measuring impact load parameters from 17 fresh pig heads that were shot at the right part of cranium by a standard 7.62 mm M43 bullet. FE analysis was executed through the LS-DYNA code under impact loads similar to those obtained from the experimental study. The residual velocity, the transferred energy from the bullet to the cranium, and the surface area of the entrance showed no statistical differences between the FE simulation and the experimental study. However, the mean surface area of the exit wounds was significantly larger than that of the entrance wounds in the experimental and FE study. Although the results of FE analysis corresponded with the experiment study, FE analysis further revealed that the stress zones were mainly located at the impact region of the cranium, mainly located in occipital lobe, frontal lobe and skull base of brain, with a lower speed of stress distribution. The FE model was appropriate and conformed to the basic principles of wound ballistics. © IOS Press and the authors. All rights reserved.

Li B.C.,Chongqing Medical University | Li B.C.,State Key Laboratory of Trauma | Li Y.,Kunming Medical University | Chen L.F.,Chongqing Medical University | And 4 more authors.
Journal of the Neurological Sciences | Year: 2011

In recent years, olfactory ensheathing cells (OECs) have been used as a therapeutic strategy to repair the anatomical structure and promote the function recovery of injured spinal cord in both animal and human. In this study, OECs were transplanted into contused spinal cords of adult rats. After dorsal laminectomy at T10 vertebra, spinal cord was injured by a force of 10 g with NYU II impactor from 25 mm above the exposed cord. The contused spinal cord received injections of OECs in DMEM or DMEM alone at one week after injury. The migration and distribution of OECs in the contused spinal cord were observed by the light microscope. The intact tissue area, injured tissue area, cavity size, number of myelinated nerve fibers and neurons labeled by CB-HRP in T8 segment were measured and counted by the semi-quantitative techniques at 6 weeks after transplantation. Locomotor ability and conductive function of the spinal cord were evaluated by the BBB score and cortical somatosensory evoked potentials (CSEP) recording. OECs were found in both lesion site and tissue near the lesion. The intact tissue area was significantly larger in the OECs-transplanted rats than that in the DMEM-injected animals, whereas the injured tissue area was significantly smaller in the OECs-rats than that in the DMEM-rats. The number of myelinated nerve fibers in the lesion site and preserved neurons in T8 was significantly greater in the OECs-group than in the DMEM-group, but the cavity size detected was not significantly different between the two groups. The BBB score and CSEP recording showed a better performance of locomotor ability and conductive function in the OECs-transplanted rats than in the DMEM-injected animals. These results indicate that OECs can counteract secondary tissue degeneration after spinal cord injury. Although they cannot reduce the cavity formation, they can promote morphological preservation and functional improvement of the contused spinal cord. © 2011 Elsevier B.V.

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