Abstract Purpose To investigate the effect of urocortin-1 (UCN-1) on the growth, migration and apoptosis of colorectal cancer (CRC) in vivo and vitro and mechanism of UCN-1 modulating CRC cells in vitro. Methods The correlation between UCN-1 and CRC was evaluated by Cancer Genome Atlas (TCGA) database and the tissues microarray. The expression of UCN-1 in CRC cells was explored by quantitative real-time polymerase chain reaction (RT-qPCR) or western blot. In vitro, the influence of UCN-1 on proliferation, apoptosis and migration HCT-116 and RKO cells were explored by celigo cell counting assay, flow cytometry and wound healing assay or transwell, respectively. In vivo the effect of UCN-1 on CRC tumor growth and progression was evaluated in the nude mice. The downstream pathway behind UCN-1 regulating CRC was found by phospho-kinase profiler array in RKO cells. Expression of UCN-1 in cells was knocked down or upregulated using lentivirus. Results Both of the results of TCGA database and the tissues microarray shown that UCN-1 strongly expressed in tissues of CRC patients. Furthermore, the tissues microarray results showed that expression of UCN-1 was higher in male CRC patients than that in female patients, and high expression of UCN-1 was associated with higher risk of lymphatic metastasis and later pathological stage. Additionally, knockdown of UCN-1 in CRC cells caused a reduction in cell proliferation, migration, and colony formation as well as an increase in apoptosis. In xenograft experiments, tumors generated from RKO cells with UCN-1 knockdown exhibited declined tumor volume and weight. Reduction of the expression of Ki67 in xenograft tumors reflected that knockdown of UCN-1 curbed the growth of CRC tumors. Furthermore, the human phospho-kinase array showed that p53 signal pathway participated in UCN-1-mediated CRC development. The suppression in migration and proliferation caused by UCN-1 knockdown was reversed by inhibitors of p53 signal pathway, while the increase of cell apoptosis was withdrawn. On the other hand, overexpression of UCN-1 promoted the proliferation and migration and inhibited apoptosis of CRC cells. Overexpression of p53 reversed the effect of UCN-1 overexpression on CRC development. Conclusion UCN-1 promotes the migration, proliferation and inhibits apoptosis via inhibition of p53 signaling pathways.
Motilin is a gastrointestinal hormone that is mainly produced in the duodenum of mammals, and it is responsible for regulating appetite. However, the role and expression of motilin are poorly understood during starvation and the weaning stage, which is of great importance in the seeding cultivation of fish. In this study, the sequences of Yangtze sturgeon (Acipenser dabryanus Motilin (AdMotilin)) motilin receptor (AdMotilinR) were cloned and characterized. The results of tissue expression showed that by contrast with mammals, AdMotilin mRNA was richly expressed in the brain, whereas AdMotilinR was highly expressed in the stomach, duodenum, and brain. Weaning from a natural diet of T. Limnodrilus to commercial feed significantly promoted the expression of AdMotilin in the brain during the period from day 1 to day 10, and after re-feeding with T. Limnodrilus the change in expression of AdMotilin was partially reversed. Similarly, it was revealed that fasting increased the expression of AdMotilin in the brain (3 h, 6 h) and duodenum (3 h), and the expression of AdMotilinR in the brain (1 h) in a time-dependent manner. Furthermore, it was observed that peripheral injection of motilin-NH2 increased food intake and the filling index of the digestive tract in the Yangtze sturgeon, which was accompanied by the changes of AdMotilinR and appetite factors expression in the brain (POMC, CART, AGRP, NPY and CCK) and stomach (CCK). These results indicate that motilin acts as an indicator of nutritional status, and also serves as a novel orexigenic factor that stimulates food intake in Acipenser dabryanus. This study lays a strong foundation for the application of motilin as a biomarker in the estimation of hunger in juvenile Acipenser dabryanu during the weaning phase, and enhances the understanding of the role of motilin as a novel regulator of feeding in fish.
One of the challenging task for the human visual system is how they extract and integrate the local elements from the cluttered background into the global contour perception. Although previous studies have suggested the involvement of both striate and extrastriate cortex for this intermediate-level processing of visual perception, their relative roles and dynamic interactions between these areas are largely unknown. To examine whether the recurrent processing between the lower and higher-level visual areas plays a causal role in contour integration, we applied fMRI-guided transcranial magnetic stimulation (TMS) on early visual cortex (V1/V2) and intermediate-level visual area (V3B) at four SOAs (60/80, 90/110, 120/140 or 150/170 ms) (plus a no-TMS condition) while the participants performed a contour detection task. Results showed that both V1/V2 and V3B were critically involved in the process of contour integration. Importantly, the first critical inference time window for V1/V2 (120/140 ms, p < .05, Cohen's d = 0.57) follows that for V3B (90/110 ms, p < .05, Cohen's d = 0.58). The inference effect was also found at 150/170 ms for both areas (V1/V2: p = .05, Cohen's d = 0.50; V3B: p = .08, Cohen's d = 0.41). These findings suggested that the critical contribution of V3B to contour integration was earlier than that of V1/V2. The present study provides direct evidence supporting the causal role of the recurrent processing between V3B and V1/V2 in contour integration and agree with the data from monkey physiology. Our findings fit well with the incremental grouping theory (Roelfsema, 2006; Roelfsema & Houtkamp, 2011), in which a feedforward sweep generates a coarse template in higher visual areas with large receptive fields before the processing of detail information in lower visual areas with small receptive field through feedback mechanisms. Meeting abstract presented at VSS 2017
In this paper,we study the effects of chronic stress on the spatial learning-memory function of mice,and the expression of glial cell line-derived neurotrophic factor(GDNF) in mice's brain.The ability of spatial learning-memory of mice′s were determined by Morris water maze task,and the expression of GDNF in the hippocampus(HP) and prefrontal cortex(PFC) were detected by immunohistochemical method.The results showed that the ability of spatial learning and memory were significantly decreased(P0.01) in the stress group mice,compared with the control group mice.The GDNF expression in the CA1,CA3 and dentate gyrus of HP and PFC were significantly reduced in the stress group mice(P0.05,P0.01) on after stress and 7 days after stress period.The results suggested that chronic stress causes the damage of spatial learning and memory function in mice which may be nearly related to the changes of GDNF expression.
Abstract Biomolecule sulfation catalyzed by sulfotransferases (STases) plays a profound role in numerous biological processes. However, the exact biofunctions of the sulfation modifications still remain largely unknown partially because STases are difficult to assay. Most of the existing STase assays are targeted to discriminate the property changes of the sulfated substrate against the un‐sulfated ones, which typically suffer from several drawbacks due to the labile sulfated products, inhibitory effect of the 3'‐phosphoadenosine‐5'‐phosphate (PAP) by‐product as well as the lack of generality. To address such issues, herein, we have developed a versatile and general fluorescence turn‐on strategy for assaying STase activities. Unlike traditional STase assays, this work is targeted to measuring the phosphate ion (Pi) released from the enzymatic degradation of PAP by‐product during the sulfation reaction, which can lead to fluorescence enhancement of a calcein/Ce 3+ system. Since PAP is the common by‐product of all kinds of STase reactions, this assay is universally applicable to the varying kinds of STases. In this regard, the intrinsic instability of the sulfated substrates will no longer influence the assay accuracy. Furthermore, the inhibitory effect of PAP on the STase reaction, which is common in traditional STase assays, are effectively removed in this study, thereby allowing more accurate determination of the enzyme activity.
Objective To explore the effect of behavior training on the proliferation of neural stem cells in the dental gyrus(DG) of hippocampus injury-infarcted rats.Methods One hundred and eight Sprague-Dawley rats were randomized into behavior training group(1,7,14,21,28 and 35 days),no-training group(1,7,14,21,28 and 35 days) and control group(1,7,14,21,28 and 35 days).Photochemical initiation was used to induce hippocampal injury-infarction in training and no-training group.Morris water maze training or no-training was performed 1 day after surgery.Double staining immunofluorescence was used to detect the expression of BrdU/Nestin in the dental gyrus(DG) at different time points.Results Few BrdU/Nestin double staining cells were observed in the DG of control rats.In the behavior training and no-training groups for 7,14,21 and 28 days,the number of BrdU/Nestin double-stained cells increased in the DG on the opposite side compared with the control group(P0.01).BrdU/Nestin double-stained cells increased obviously after 7,14,21 and 28 days in the behavior training group compared with the no-training group(P0.01).In the behavior training and no-training groups for 35 days,no significant difference of the number of BrdU/Nestin double-stained cells in the DG on the opposite side was found between them and the control group(P0.05).Conclusion Behavior training can accelerate the proliferation of neural stem cells and then encourage the recovery of neural function.
Objective To study the relationship between cerebral hemorrhage and the change in the level of neurotensin (NT) for the purpose of making prognoctic judgement of acute cerebral injury and optimizing nutritional nursing care for the patients. Methods Cerebral hemorrhage animal model was established in dogs to observe the changes of NT content in plasma and gastric juice preprandially and postprandially after the injury, Results in the initial stages of cerebral injury, the concentration of NT in plasma increased, but recovered the normal level gradually when the condition was brought to stability. Postprandially, NT can be released into blood circulation and manifest hormonal property. Conclusion Changes in NT level are closely related with cerebral hemorrhage. Lipid plays an important role in the stimulation of NT secretion, in the process of which amino acid and glucose take no part,
Previous literature suggests that low-level stimulus properties determine the detection performance of contours and are used to define different contour types. Here we investigated the processing of different types of contours under conscious and unconscious conditions. In Experiment 1, we adopted an inattentional blindness paradigm and showed that collinear contours (i.e., a contour type that is frequently observed in natural images) induced a positive cuing effect in both the conscious and unconscious conditions, whereas orthogonal contours (which are less prevalent in the natural environment) attracted attention only when consciously perceived. In Experiment 2, we showed that collinear contours rendered invisible by continuous flash suppression emerged from suppression more rapidly than a random field, whereas orthogonal contours had no such breaking superiority. These results suggest that collinear but not orthogonal contours can be processed and serve as attentional cues without conscious awareness. Our findings provide further evidence that the relevance of the contours to natural statistics could be a key evolutionary factor that decides whether a contour can be unconsciously processed to increase its detectability in a clutter environment.
Objective To investigate the effect of hyperbaric oxygen (HBO) on angiogenesis in the brain of adult rats with cerebral ischemia-reperfusion injury.Methods The adult male Sprague-Dawley (SD)rats were randomly divided into 3 groups:the sham surgery (SS) group,the ischemia-reperfusion (IR) group and the HBO group,and each group was further divided into 3 subgroups:the 3- day group,the 7- day group and the 10-day group.Middle cerebral artery occlusion (MCAO) was performed on the IR and HBO groups to develop the animal model.One and half hours later,reperfusion was made.The HBO group received HBO treatment and the SS group was left there without any treatment.All the rats were sacrificed respectively on day 3,7,10 and 21.Cerebral samples were collected and treated with immunohistochemical staining for the monitoring of vascular endothelial growth factor (VEGF),VEGF receptor-1 (VEGFR-1) and CD34.The changes in the ischemia region were observed under the optical microscope,and pictures were taken.Results When compared with those of the SS group,counts of VEGF and VEGFR-1 and SD34 positive cells increased markedly in the IR group (P ＜ 0.05 ).Following HBO treatment,counts of VEGF,VEGFR-1 and SD34positive cells in the animals of the HBO group increased significantly on day 7 and 10,when compared with those of the IR group (P＜0.05).For the 10-day sub-group in the IR group,counts of VEGF were 17.3 ±2.6,those of VEGFR-1 18.5 ± 2.9 and those of CD34 11.3 ± 2.7 ; for the 10-day sub-group in the SS group,counts of VEGF were 4.2 ±0.8,those of VEGFR-1 4.2 ±0.3 and those of CD34 3.6 ±0.6; and for the 10-day sub-group in the HBO group,counts of VEGF were 43.6 ± 5.5,those of VEGFR-1 36.5 ± 5.8 and those of CD34 43.6 ±5.5.Conclusions HBO therapy could effectively promote angiogenesis of micro vessels in the brain of adult rats with ischemia-reperfusion injury.
Key words:
Hyperbaric oxygen; Middle cerebral artery occlusion; Angiogenesis; VEGF; VEGFR-1
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