ABSTRACT
Pituitary tumors are usually benign but can occasionally exhibit hormonal and proliferative behaviors. Dysregulation of the G1/S restriction point largely contributes to the over-proliferation of pituitary tumor cells. F-box protein S-phase kinase-interacting protein-2 (SKP2) reportedly targets and inhibits the expression of p27(Kip1), a well-known negative regulator of G1 cell cycle progression. In this study, SKP2 expression was found to be upregulated while p27(Kip1) expression was determined to be downregulated in rat and human pituitary tumor cells. Furthermore, SKP2 knockdown induced upregulation of p27(Kip1) and cell growth inhibition in rat and human pituitary tumor cells, while SKP2overexpression elicited opposite effects on p27(Kip1) expression and cell growth. The expression of microRNA-186 (miR-186) was reported to be reduced in pituitary tumors. Online tools predicted SKP2 to be a direct downstream target of miR-186, which was further confirmed by luciferase reporter gene assays. Moreover, miR-186 could modulate the cell proliferation and p27(Kip1)-mediated cell cycle alternation of rat and human pituitary tumor cells through SKP2. As further confirmation of these findings, miR-186 and p27(Kip1) expression were downregulated, while SKP2 expression was upregulated in human pituitary tumor tissue samples; thus, SKP2 expression negatively correlated with miR-186 and p27(Kip1) expression. In contrast, miR-186 expression positively associated with p27(Kip1) expression. Taken together, we discovered a novel mechanism by which miR-186/SKP2 axis modulates pituitary tumor cell proliferation through p27(Kip1)-mediated cell cycle alternation.
Subject(s)
Animals , Humans , Rats , Cell Cycle , Cell Proliferation , Cyclin-Dependent Kinase Inhibitor p27 , Genes, Reporter , Luciferases , Pituitary Neoplasms , Up-RegulationABSTRACT
Objective To investigate the the preventive and management methods of pure-NOTES transanal total mesorectal excision (pure-NOTES TaTME) with postoperative anastomotic complications.Methods Retrospectively analyzed the clinical data of 59 cases with low and middle rectal cancer who were underment pure-NOTES TaTME in Linzi District People's Hospital,and discussed the situction of the complications.Results Postoperative anastomotic complications were occurred in 3 cases,anastomotic leakage in 1 case,anastomotic stenosis in 1 case,anastomotic stenosis and leakage in 1 case,accounting for 5.1％.Conclusions For suitable rectal neoplasms patients,pure-NOTES TaTME operation doesn't increase the incidence of anastomotic complication,and it's is safe and feasible.Preoperative preparation,good blood supply,tension-free anastomosis,and correct choice and using of stapler and anastomotic drainage tube are the key to reduce anastomotic complications.
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Objective To observe the expression of protein AQP5 and CC16 in lung after hemorrhagic shock resuscitation in rats in order to explore the mechanism of acute lung injury.Methods Thirty-two healthy and clean male SD rats were randomly (random number) divided into two groups:control group and hemorrhagic shock resuscitation group (n =16 in each).Besides,each group was further divided into two subgroups according to the experiment done at 12 h and 24 h after hemorrhagic shock resuscitation (n =8).The hemorrhagic shock model was made by using Wiggers' modified method.Resuscitation was done by transfusing the autologous blood and the equal volume of Ringer's solution.Blood samples were obtained from abdominal aorta at each given interval to measure the level of plasma endotoxin,and assay the CC16 and AQP5 by using ELISA.After the rats were sacrificed,the left lung tissue was taken to measure lung water content and the dry/wet ratio,and to examine the levels of CC16 and AQP5 in lung tissue by immunohistochemical method.Results ①The level of plasma endotoxin in the experimental group was significantly higher than that in the control group (P ＜ 0.01).②The content of plasma CC16 in the experimental group was higher than that in the control group (P ＜ 0.05).③Compared with the control group,the content of pulmonary homogenate AQP5 in the experimental group was significantly lower (P ＜0.05).④The lung water content (the dry/wet ratio) of the experimental group was obviously higher than that of the control group (P ＜ 0.05).⑤Hislogogical observation with HE staining showed in the control group,the alveolar structure was complete,the alveolar sacs were clear,and the alveolar septum was intact;but in the experimental group,the alveolar septum was widened,and there were obvious hemorrhage and neutrophil infiltration in the alveolar space.⑥ The level of lung tissue CC16 in control group was significantly higher compared with experimental group (P ＜ 0.05).⑦ The level of lung tissue AQP5 was significantly higher in control group compared with experimental group (P ＜ 0.05).Conclusions The proteins of AQP5 and CC16 were involved in the process of acute lung injury after hemorrhagic shock resuscitation in rats,and their levels were positively correlated with length of time after hemorrhagic shock.
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Background In recent years,some researches had been conducted on the pathologic changes of the secondary injury of perihematoma in animal experiments,but only a few studies had been done on the dynamic pathologic and ultrastructural changes of the perihematoma in ICH patients. The unique contribution of our study is to investigate the dynamic pathologic and ultrastructural changes of the perihematoma in ICH patients and provide significant insights into how the pathophysiology and ultrastructures changed after ICH.Methods The written informed consents were obtained from the ICH patients or their relatives. 30 patients (the supertentorial hemotoma volume＞30 mi and the cerebellar hemotoma volume ＞10 mi) were divided into 8 groups according to the time passed after ICH:＜6 h (6 patients), 6 ～ 12 h (7 patients), 12 ～24 h (5 patients), 24～48 h (3 patients), 48 ～72 h (3 patients), 3 ～4 days group (3 patients), 5 days group (2 patients) and 8 days group ( 1 patient) and subjected to craniotomy for hemotoma evacuation. During the operation for the hemotoma's evacuation, a small amount of tissues that must be removed, which located at 1 cm near the hematoma, were taken as experimental groups; And the same tissues of 7 patients (＜12 h), which were far from the hemotoma on the operational way, were taken as control group. The pathologic and ultrastructral changes were observed.Results The tissues of the control group were almost normal while the damages of the tissues from the experimental groups were slight in ＜6 h groups, more severe after 6h and got to the maximum between 24 ～48 h , recovered gradually after 72 h, became similar to the 6 ～ 12 h group on 5 th day, got better on 8 th day and resembled the 6 h group.Conclusions The injury of the perihematoma occurred in early stage, reached the peak level between 24 and 48 hours after ICH; which was consistent to the clinical nervous functional deficits in the ICH patients.
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72 h goups, respectively. A few tissues distant from the hematoma on the way into the cranium were taken from the 2 former groups as control. Immunohistochemistry staining and reverse transcription polymerase chain reaction (RT-PCR) were used to detected expression of complement facters C3 ,complement inhibitor (Clusterin),the infiltration of the inflammatory cells, the proliferation of neuroglia cells and the expression of cytokins.Results The immunohistochemistry staining showed that the expression of complement facter C3 got to the peak at 12~72 h (P