ABSTRACT
The molecular mechanism of cleft lip and palate has been a hot topic for research in recent years. With the development of genetic technology, more than 100 genes have been associated with cleft lip and palate, though the pathological mechanism of such genes has not been delineated.The information carried by each of these genes may affect the phenotype through signal pathway, and abnormal function of these signal pathways has been found in the formation of cleft lip and palate. A series of signal factors have known to involve in the regulation of gene expression, and may interact with each other to form complex signal regulatory networks which are involved in the guidance of cell activity and tissue formation. This article has summarized several signal pathways related to lip and palate, and the molecular mechanism underlying the development of lip and palate.
ABSTRACT
The aim of this study was to investigate the possible beneficial role of telmisartan in cerebral edema after traumatic brain injury (TBI) and the potential mechanisms related to the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) pyrin domain-containing 3 (NLRP3) inflammasome activation. TBI model was established by cold-induced brain injury. Male C57BL/6 mice were randomly assigned into 3, 6, 12, 24, 48 and 72 h survival groups to investigate cerebral edema development with time and received 0, 5, 10, 20 and 40 mg/kg telmisartan by oral gavage, 1 h prior to TBI to determine the efficient anti-edemic dose. The therapeutic window was identified by post-treating 30 min, 1 h, 2 h and 4 h after TBI. Blood-brain barrier (BBB) integrity, the neurological function and histological injury were assessed, at the same time, the mRNA and protein expression levels of NLRP3 inflammasome, IL-1β and IL-18 concentrations in peri-contused brain tissue were measured 24 h post TBI. The results showed that the traumatic cerebral edema occurred from 6 h, reached the peak at 24 h and recovered to the baseline 72 h after TBI. A single oral dose of 5, 10 and 20 mg/kg telmisartan could reduce cerebral edema. Post-treatment up to 2 h effectively limited the edema development. Furthermore, prophylactic administration of telmisartan markedly inhibited BBB impairment, NLRP3, apoptotic speck-containing protein (ASC) and Caspase-1 activation, as well as IL-1β and IL-18 maturation, subsequently improved the neurological outcomes. In conclusion, telmisartan can reduce traumatic cerebral edema by inhibiting the NLRP3 inflammasome-regulated IL-1β and IL-18 accumulation.
Subject(s)
Animals , Humans , Male , Mice , Benzimidazoles , Benzoates , Blood-Brain Barrier , Brain Edema , Drug Therapy , Genetics , Pathology , Brain Injuries, Traumatic , Drug Therapy , Genetics , Pathology , Caspase 1 , Gene Expression Regulation , Inflammasomes , Genetics , Interleukin-18 , Interleukin-1beta , NLR Family, Pyrin Domain-Containing 3 Protein , Genetics , Signal TransductionABSTRACT
Objective To quantitatively study the posterior fossa effective space and its relationship with hemifacial spasm (HFS).Methods We conducted a case-control study of patients diagnosed with HFS and sex-and age-matched healthy controls.All subjects underwent high-resolution three-dimensional MRI.The software of 3D-Slicer was used to measure the posterior fossa space and hindbrain tissue volume between the two groups.Results Sixty patients and 60 controls were enrolled in this study.Compared to controls,patients with HFS had a higher posterior fossa crowdedness index (PFCI;83.7％ ± 0.6％ vs 79.2％ ± 0.4％;t =2.58, P =0.01).The multivariate linear regression analysis revealed that a higher PFCI was associated with younger age (r =-0.61, P =0.02), female gender (r =0.76, P =0.003) and HFS (r =-0.43, P =0.01).Conclusions Patients with HFS have a more crowded posterior fossa space than healthy controls, potentially leading to cranial nerve and vascular structure crowding, thus increasing HFS risk.Women have a higher PFCI, which may explain the strong female preponderance in epidemiologic studies.
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Objective To investigate the effect of olfactory entheath cells (OECs) transplantation on neural function and synaptic density of rats with traumatic brain injuries (TBI) and the possible mechanism. Methods Rats were divided into sham operation group, TBI group and OECs engrafted group. The brains of the rats were injured by Feeney percussion device through free falling. After cultured and identified by using specific marker (known as P75), OECs were transplanted into the area around the injured brain. Cortical somatosensory evoked potential (CSEP) and motor evoked potential ( MEP) were evaluated at day 14 after cell transplantation to determine the neurophysiologic function following TBI. Moreover, the synaptic densities around the injured brain were determined by using immunohistochemical method. One-way ANOVA test was used for statistical analysis. Results The transplanted OECs could survive and migrate around the injury site in the host brain 14 days after OECs transplantation. In addition, rats subjected to OECs implantation showed a marked neurophysiologic improvement and a significant increase of synaptic densities compared with the control group. Conclusion OECs transplantation can improve the neurophysiologic function and increase the synaptic density, which provides experimental basis for treatment of TBI with OECs.
ABSTRACT
Objective To establish contusion brain injury model in rats, and investigate the efficacy of intravenous administration of neural stem cells(NSC) on posttraumatic neurocognitive function recovery and NGF expression in rats. Methods Cerebral contusion model in motor-sensory cortex of the right parietal cortex in rat was established by a 50 g-weight hammer falling respectively from 30 cm height along guide stick to impact collision pole by improved trauma device for model of contusion brain injury based on Feeney method. And the NSC isolated from GFP transgenic mice were injected intravenously via the tail vein 24 h after the brain trauma, and 1 week later neurocognitive function scores and NGF immunostaining were performed to explore the efficacy of NSC transplant. Results The NSCs from the GFP transgenic mice gathered at the injury site 1 weeks after transplants.Neurocognitive function scores and NGF-positive cells measurement(226 ±27,23 ±4 ) in the treatment group revealed significant increase than in the brain trauma group(300 ±36;15 ±3 )(P＜0.05). Conclusion The intravenous NSC injection in rats can survive and migrate to the injured brain region and promote the post-injury neurocognitive function restoration. The increase of NGF expression may underline one of most important mechanisms in NSC treatment' s rats after brain injury.