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As a ligand-dependent transcription factor,retinoid-associated orphan receptor γt(RORyt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the pro-gression of several inflammatory and autoimmune conditions.An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORyt to decrease Th17 cell development and IL-17 production.Several RORyt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORyt by binding to orthosteric-or allosteric-binding sites in the ligand-binding domain.Some of small-molecule inhibitors have entered clinical evaluations.Therefore,in current review,the role of RORyt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted.Notably,the recently developed RORyt inhibitors were summarized,with an emphasis on their optimization from lead compounds,ef-ficacy,toxicity,mechanisms of action,and clinical trials.The limitations of current development in this area were also discussed to facilitate future research.
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Purpose@#Acute kidney injury (AKI) is a serious complication of sepsis and is characterized by inflammatory response. MicroRNA-210 host gene (MIR210HG) is upregulated in human proximal tubular epithelial cells under treatment of inflammatory cytokines. This study aimed to explore the role of MIR210HG in sepsis-induced AKI. @*Materials and Methods@#Cell viability was detected by a cell counting kit 8 assay. The levels of proinflammatory cytokines were detected by enzyme-linked immunosorbent assay kits. The protein levels of p65, IκBα, and p-IκBα were examined by western blot analysis. The nuclear translocation of nuclear factor kappa B (NF-κB) was detected by immunofluorescence assay. The histological changes of kidneys were analyzed by hematoxylin and eosin staining assay. @*Results@#Lipopolysaccharide (LPS) treatment significantly inhibited cell viability and increased productions of proinflammatory cytokines in proximal tubular epithelial cells (HKC-8). Additionally, MIR210HG levels in HKC-8 cells were increased by LPS treatment. MIR210HG silencing inhibited the LPS-induced cell inflammatory response. MIR210HG activated the NF-κB signaling pathway by promoting the phosphorylation of IκBα and nuclear translocation of p65. Rescue assays revealed that the MIR210HGinduced increase of cytokines levels and decline of cell viability were rescued by QNZ treatment. Knockdown of MIR210HG decreased blood urea nitrogen, serum creatinine, and proinflammatory cytokine levels in AKI rats. Moreover, the knockdown of MIR210HG protected against AKI-induced histological changes of kidneys in rats. @*Conclusion@#MIR210HG promotes sepsis-induced inflammatory response of HKC-8 cells by activating the NF-κB signaling pathway. This novel discovery may be helpful for the improvement of sepsis-induced AKI.
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Purpose@#Acute kidney injury (AKI) is a serious complication of sepsis and is characterized by inflammatory response. MicroRNA-210 host gene (MIR210HG) is upregulated in human proximal tubular epithelial cells under treatment of inflammatory cytokines. This study aimed to explore the role of MIR210HG in sepsis-induced AKI. @*Materials and Methods@#Cell viability was detected by a cell counting kit 8 assay. The levels of proinflammatory cytokines were detected by enzyme-linked immunosorbent assay kits. The protein levels of p65, IκBα, and p-IκBα were examined by western blot analysis. The nuclear translocation of nuclear factor kappa B (NF-κB) was detected by immunofluorescence assay. The histological changes of kidneys were analyzed by hematoxylin and eosin staining assay. @*Results@#Lipopolysaccharide (LPS) treatment significantly inhibited cell viability and increased productions of proinflammatory cytokines in proximal tubular epithelial cells (HKC-8). Additionally, MIR210HG levels in HKC-8 cells were increased by LPS treatment. MIR210HG silencing inhibited the LPS-induced cell inflammatory response. MIR210HG activated the NF-κB signaling pathway by promoting the phosphorylation of IκBα and nuclear translocation of p65. Rescue assays revealed that the MIR210HGinduced increase of cytokines levels and decline of cell viability were rescued by QNZ treatment. Knockdown of MIR210HG decreased blood urea nitrogen, serum creatinine, and proinflammatory cytokine levels in AKI rats. Moreover, the knockdown of MIR210HG protected against AKI-induced histological changes of kidneys in rats. @*Conclusion@#MIR210HG promotes sepsis-induced inflammatory response of HKC-8 cells by activating the NF-κB signaling pathway. This novel discovery may be helpful for the improvement of sepsis-induced AKI.
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Objective:To analyze the expression of microRNA-23a (miR-23a) and phosphatase and tensin homolog detected on chromosome ten (PTEN) regulatory axis in LS513 cells, and to explore the effects of miR-23a and PTEN on the occurrence and development of CRC.Methods:LS513 cells were divided into blank control group (NG group) : cells were not specially treated, negative control group (NC group) : 5 μl Lipofectamine3000 and 50 pmol/μl NC were added, Inhibition of miR-23a expression group (miR-23a-inhibitor group) : miR-23a-inhibitor sequence was transfected. The mRNA levels of miR-23a and PTEN in LS513 cells were detected by real-time fluorescence quantitative PCR (qRT-PCR) ; the proliferation of LS513 cells was detected by MTT method; Transwell assay was used to detect cell migration and invasion; Western blotting was used to detect proliferation, migration, invasion and phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) signaling pathway related proteins.Results:Compared with those in NG group and NC group, the level of miR-23a in miR-23a inhibitor group was significantly lower ( P<0.05) , and the expression levels of PTEN mRNA and protein were significantly higher ( P<0.05) . The results of MTT showed that, compared with those in NG group and NC group, the proliferation inhibition rate in miR-23a-inhibitor groupwas significantly higher ( P<0.05) , and the expression of PCNA protein was significantly lower ( P<0.05) . Compared with those in NG group and NC group, the migration number and invasion number of LS513 cells in miR-23a-inhibitor group were significantly lower ( P<0.05) , and the expression of MMP-9 and E-cadherin protein was significantly lower ( P<0.05) . Compared with those in NG group and NC group, the expression of p-pi3k/PI3K and p-atk/ATK protein in miR-23a-inhibitor group was significantly lower ( P<0.05) . Conclusion:Inhibition of miR-23a expression may up-regulate PTEN gene expression, inhibit PI3K/Akt pathway activation, and then inhibit the proliferation, migration and invasion of LS513 cells.
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This paper discussed the development of hospice care in our country form five respects , detailed e-laborated our country the main manifestations of lacking hospice medical service policy : relevant policies render fragments;relevant policy interoperability is not strong;Relevant policy lack of financial support;the lack of pub-licity related policy .On this basis , put forward the hospice career development needs of related policies , inclu-ding:set up complete medical security system;establish perfect hospice service classification management mecha-nism;establish and perfect the government funds allocated for hospice care medical services .
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<p><b>BACKGROUND</b>Rathke's cleft cyst (RCC) is one of the most common incidentally discovered sellar lesions, while symptomatic cases are relatively rare. Surgical treatment is recommended for symptomatic patients to drain the cyst content and to remove the capsule safely. The aim of this study was to clarify the clinical features, surgery considerations and therapy outcomes of symptomatic RCCs.</p><p><b>METHODS</b>Totally 42 patients (19 males and 23 females) were retrospectively reviewed with the diagnosis of RCCs under surgery resection at the Affiliated Hospital of Medical College, Qingdao University between January 2005 and December 2010.</p><p><b>RESULTS</b>Patients' age ranged from 6 to 67 years (mean of 41.6 years). The duration of symptoms ranged from 4 days to 10 years. Headache (69%), visual impairment (36%), and pituitary dysfunction (10%) were the most common presenting symptoms. The maximum diameter of cysts ranged from 6.0 to 46.7 mm (mean of 20.07 mm). Of the 42 patients, 36 underwent endonasal transsphenoidal approach and the others underwent transcranial approach. Thirty patients had a subtotal resection and decompression, while 12 patients had a total cyst resection. Cysts of 28 patients were lined by simple cubical or columnar epithelium, and cysts of 34 patients were filled by amorphous colloid material, that was the characteristic of RCCs. The majority of patients presented with a simple headache, and 93% of this group experienced a complete improvement after surgery. Twelve of 15 patients (80%) with preoperative visual deficits experienced an improvement in their vision after surgery. All of those patients with pituitary dysfunction experienced an improved endocrine status. The endocrinological complication usually was diabetes insipidus, and postoperative transient diabetes insipidus occurred in 13 (31%) patients without any permanent diabetes insipidus. The overall recurrence rate was 7% at a mean follow-up of 22 months (range 12 - 60 months).</p><p><b>CONCLUSIONS</b>Surgical treatment is to drain the contents of the cyst and to remove the capsule as much as possible under the precondition that does not increase the complications. Biopsy and decompression procedures are recommended for most cases.</p>