Abstract Hypoxia preconditioning (HPC), a well-established preconditioning model, has been shown to protect the brain against severe hypoxia or ischemia caused by traumatic brain injury (TBI), but the mechanism has not been well elucidated. Anaerobic glycolysis is the major way for neurons to produce energy under cerebral ischemia and hypoxia after TBI, and it requires large amounts of glucose. We hypothesized that glucose transport, as a rate-limiting step of glucose metabolism, may play key roles in the neuroprotective effects of HPC on cerebral cortex tissue against TBI. The aim of this study was to investigate the effect of HPC on glucose transport activity of rat cerebral cortex tissue after TBI through examining the gene expression of two major glucose transporters (GLUT1 and GLUT3) and their upstream target gene hypoxia-inducible factor-1α (HIF-1α). Sprague-Dawley rats were treated with HPC (50.47 kPa, 3 h/d, 3d). Twenty-four hours after the last treatment, the rats were injured using the Feeney free falling model. Cortex tissues of injured rats were removed at 1 h, 4 h, 8 h, 12 h, 1 day, 3 days, 7 d, and 14 days post-injury for histological analysis. Compared with TBI alone, HPC before TBI resulted in the expression of HIF-1α, GLUT1, and GLUT3 to increase at 1 h; they were markedly increased at 4 h, 8 h, 12 h, 1 day, and 3 days and decreased thereafter ( p < 0.05). HPC before TBI could improve neuronal survival in rats by examining NeuN staining and observing reduced apoptosis by examining TUNEL staining. The result showed that HPC before TBI could increase the expression of GLUT1 and GLUT3. And through double immunofluorescence staining for GLUT3 and NeuN, the results strongly suggest that HPC improved glucose transport activity of neurons in rats with TBI. In summary, our results further support that HPC can improve hypoxia tolerance and attenuate neuronal loss of cerebral cortex in rats after TBI. The mechanism is mainly related to the increase of glucose transport activity through inducing GLUT1 and GLUT3 expression through upregulating HIF-1α expression.
Objective To explore the effect ofhypoxic preconditioning (HPC) on the expression of sphingosine kinase-1 (SphK-1) and blood-brain barrier (BBB) permeability in rats after traumatic brain injury (TBI).Methods Two hundred and four SD rats were randomly assigned into TBI group (n=96),HPC group (giving HPC and TBI,n=96) and blank control group (n=12).The rats in the TBI group were subjected to TBI with freefall impact method,while the rats of HPC group were treated with the same methods after HPC (50.47 kpa,3 d,3 h/d).And then,they were sacrificed at each time point (1,4,8 and 12 h,and 1,3,7 and 14 d after injury).RT-PCR and Western blotting were employed to detect the mRNA and protein expression changes of SphK-1 in brain contusion area at each time points after injury.Immumohistochemical staining (IgG method) was used to detect the BBB permeability changes of the rats.Results IgG scores and Sphk-1 mRNA and protein expressions in rats of TBI group and HPC group began to increase at 1 h after injury and reached the highest level 1 d after injury; they were still higher than the normal levels,with significant differences (P＜0.05); SphK-1 mRNA and protein expressions in all the three groups had the same increased trend at all the time points excepted on the 14th d of injury,with significant differences (P＜0.05).IgG scores showed that the BBB permeability in the TBI group at each time point was significantly higher than that in the HPC group (P＜0.05).Conclusion Hypoxic preconditioning can increase SphK-1 expressions after TBI to promote sphingosine 1-phosphate sphingosine transformation so as to protect of the integrity of BBB.
Key words:
Hypoxic preconditioning; Traumatic brain injury; Blood brain barrier; Sphingosine kinase 1
Background: Liver metastasis (LM) in triple-negative breast cancer (TNBC) patients is associated with significant morbidity and mortality. This research aimed to develop a nomogram to predict the survival of patients with TNBC with LM (TNBC-LM).Results: A nomogram was constructed and validated to predict the overall survival (OS) of TNBC-LM patients. For patients with LM diagnosed at the initial treatment or later treatment stage, the C-index (0.739, 0.707 and 0.699 in the training, validation and extended groups, respectively) and calibration plots showed acceptable prognostic accuracy and clinical applicability of the model. Surgery on the primary tumour and chemotherapy were found to confer significantly better OS.Conclusion: We developed a sensitive and discriminative nomogram to predict OS in TNBC-LM patients, both at and after initial diagnosis.
However, it is still difficult for clinicians to establish prognostic stratifications and therapeutic strategies because of the lack of tools for predicting the survival of triple-negative breast cancer patients with liver metastases (TNBC-LM). Based on clinical data from large populations, a sensitive and discriminative nomogram was developed and validated to predict the prognosis of TNBC patients with LM at initial diagnosis or at the later course.Introduction/backgroundLiver metastasis (LM) in TNBC patients is associated with significant morbidity and mortality. The objective of this study was to construct a clinical model to predict the survival of TNBC-LM patients.Materials and methodsClinicopathologic data were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and the Fifth Affiliated Hospital of Sun Yat-Sen University (FAFSYU). Based on patients with newly diagnosed TNBC with LM (nTNBC-LM) from the SEER database, a predictive nomogram was established and validated. Its predictive effect on TNBC patients with LM at later disease course by enrolling TNBC patients from FAFSYU who developed LM later. The prognostic effect of different treatment for nTNBC-LM was further assessed.ResultsA prognostic model was developed and validated to predict the prognosis of TNBC-LM patients. For LM patients diagnosed at the initial or later treatment stage, the C-index (0.712, 0.803 and 0.699 in the training, validation and extended groups, respectively) and calibration plots showed the acceptable prognostic accuracy and clinical applicability of the nomogram. Surgical resection on the primary tumour and chemotherapy were found to be associated with significantly better overall survival (OS).ConclusionA sensitive and discriminative model was developed to predict OS in TNBC-LM patients both at and after initial diagnosis.
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