BACKGROUNDPrevious studies have suggested that long non-coding RNAs (lncRNA) TP73-AS1 is significantly upregulated in several cancers. However, the biological role and clinical significance of TP73-AS1 in pancreatic cancer (PC) remain unclear. AIMTo investigate the role of TP73-AS1 in the growth and metastasis of PC.METHODSThe expression of lncRNA TP73-AS1, miR-128-3p, and GOLM1 in PC tissues and cells was detected by quantitative real-time polymerase chain reaction. The bioinformatics prediction software ENCORI was used to predict the putative binding sites of miR-128-3p. The regulatory roles of TP73-AS1 and miR-128-3p in cell proliferation, migration, and invasion abilities were verified by Cell Counting Kit-8, wound-healing, and transwell assays, as well as flow cytometry and Western blot analysis. The interactions among TP73-AS1, miR-128-3p, and GOLM1 were explored by bioinformatics prediction, luciferase assay, and Western blot. RESULTSThe expression of TP73-AS1 and miRNA-128-3p was dysregulated in PC tissues and cells. High TP73-AS1 expression was correlated with a poor prognosis. TP73-AS1 silencing inhibited PC cell proliferation, migration, and invasion in vitro as well as suppressed tumor growth in vivo. Mechanistically, TP73-AS1 was validated to promote PC progression through GOLM1 upregulation by competitively binding to miR-128-3p. CONCLUSIONOur results demonstrated that TP73-AS1 promotes PC progression by regulating the miR-128-3p/GOLM1 axis, which might provide a potential treatment strategy for patients with PC. 相似文献
Corynebacterium species that are normally abundant on the skin and mucous membranes rarely cause infections and are susceptible to most antibiotics. The report in 1976 of four cases of sepsis at the National Institutes of Health caused by a hitherto undescribed Corynebacterium that is highly antibiotic resistant, but uniformly susceptible to vancomycin, alerted the medically oriented scientific community to the emergence of these organisms as a possible new cause of nosocomial infections. Although we have always performed antibiotic susceptibility tests on all microorganisms recovered from normally sterile body fluids, our first recovery of these organisms was in August 1977. Since then we have recovered 52 such strains from 39 patients, most frequently from the rectum, followed by the groin, blood, lesions and urine in order of predominance. Characterization by API 50 L strips revealed that most, but not all strains resemble the JK group of Riley et al. [1]. Cell wall studies and DNA base ratios further confirmed their status as corynebacteria. Hospital acquisition has been proved; cross infection between patients is the most likely mode of spread. Their recognition is necessary for optimal preventive and therapeutic care of patients with compromised host defenses. 相似文献
On activation platelets release microRNAs and extracellular vesicles (EV) into circulation. The release of EV from platelets has been shown to be dependent on the agonist; in this study, we investigated whether the microRNA profile or EV released from platelets was also agonist specific.
Washed platelets from healthy subjects were maximally stimulated with agonists specific for the receptors for collagen (Glycoprotein VI (GPVI)), thrombin (PAR1/PAR4), or ADP (P2Y1/P2Y12) with/without inhibiting secondary mediators, using aspirin to block cyclooxygenase-1 and apyrase to remove ADP. The released microRNAs were profiled using TaqMan microRNA microarray cards. Platelet-derived EV (pdEV) were characterized by size (Nanoparticle Tracking Analysis, NTA), for procoagulant activity (Annexin-V binding and support of thrombin generation), and for the EV markers CD63 and HSP70.
Platelet activation triggered the release of 57–79 different microRNAs, dependent upon agonist, with a core of 46 microRNAs observed with all agonists. There was a high level of correlation between agonists (r2 > 0.98; p < 0.0001 for all), and with the microRNA content of the parent platelets (r2 > 0.98; p < 0.0001). The 46 microRNAs seen in all samples are predicted to have significant effects on the translation of proteins involved in endocytosis, cell cycle control, and differentiation. MiR-223-3p was the most abundant in all samples and has previously been implicated in myeloid lineage development and demonstrated to have anti-inflammatory effects. Stimulation through GPVI produced a pdEV population with significantly more procoagulant activity than the other agonists. Apyrase significantly reduced microRNA and pdEV release, while aspirin had little effect.
These data suggest that all tested agonists trigger the release of a similar microRNA profile while the procoagulant activity of the pdEV was agonist dependent. ADP was shown to play an important role in the release of both microRNAs and pdEV. 相似文献
Aims/hypothesis Impaired insulin secretion has a strong genetic component. In this study we investigated whether the 12Glu9 polymorphism in the gene encoding the 2B-adrenergic receptor (ADRA2B) is associated with insulin secretion and/or the incidence of Type 2 diabetes in individuals with impaired glucose tolerance.Methods We investigated a total of 506 subjects with impaired glucose tolerance participating in the Finnish Diabetes Prevention Study (DPS). Participants were randomly assigned to an intervention group or a control group. Anthropometric measurements and an oral glucose tolerance test were performed at baseline and at annual follow-up. In a subgroup of patients (n=83), a frequently sampled intravenous glucose tolerance test (FSIGT) was performed at baseline.Results All patients had similar anthropometric measurements and insulin and glucose levels at baseline. Multiple logistic regression analysis revealed significant interaction (p=0.003) between study group and genotype across the entire study population. In the control group, subjects with the Glu9 allele had an increased risk of developing Type 2 diabetes compared with subjects with the Glu12/12 genotype (odds ratio [OR]=2.68, 95% CI 1.02–7.09, p=0.047 for Glu12/12, and OR=5.17, 95% CI 1.76–15.21, p=0.003 for Glu9/9). This increased risk was not observed in the intervention group, who showed significant weight loss during the trial. In the subgroup who underwent the FSIGT, subjects with the Glu9/9 genotype showed the lowest acute insulin response (p=0.005 for trend).Conclusions/interpretation The 12Glu9 polymorphism of ADRA2B is associated with impaired first-phase insulin secretion and may predict the development of Type 2 diabetes in subjects with impaired glucose tolerance who are not subjected to a lifestyle intervention.Abbreviations AIR acute insulin response - AR adrenergic receptor - BMR basal metabolic rate - DI disposition index - DPS the Finnish Diabetes Prevention Study - FSIGT frequently sampled intravenous glucose tolerance test - OR odds ratio - SG glucose effectiveness - SI insulin sensitivity index 相似文献
Long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) is reported to be linked to inflammation and cell apoptosis. However its role in sepsis induced kidney injury remains unclear. This study aims to explore the possible mechanism of CRNDE in kidney injury induced by sepsis. In vivo urine-derived sepsis (US) rat model and in vitro LPS-induced HK-2 and HEK293 cells were established. Kidney function was measured in rats from different groups. Relative levels of tumor necrosis factor-α (TNF-α) and interleukin-1β(IL-1β) in kidney tissue were detected via Enzyme-linked immune sorbent assay (ELISA). Then we up- or down-regulated CRNDE and miRNA-181a-5p expression in the cells. The biological influence of CRNDE and miR-181a-5p on cells was studied using CCK-8 assay and Annexin V assay. Interaction between CRNDE and miR-181a-5p was determined by bioinformatics analysis, RT-PCR, and dual luciferase reporter assay. Peroxisome proliferator-activated receptor-α (PPARα) and cell apoptosis related molecules were detected by western blot. We demonstrated that CRNDE was markedly down-regulated while miR-181a-5p was significantly up-regulated in sepsis models. CRNDE interacted with miR-181a-5p, and negatively regulated its expression level. CRNDE knockdown in rats increased the urea nitrogen and serum creatinine in plasma. Knockdown of CRNDE or transfection of miR-181a-5p significantly inhibited proliferation and promoted apoptosis of HK-2 and HEK293 cells, while overexpression of CRNDE and transfection of miR-181a-5p inhibitors had opposite effects. For mechanism, miR-181a-5p directly targeted the 3′ untranslated region of PPARα, and depressed its protein level, and PPARα was regulated indirectly by CRNDE. We concluded that CRNDE protected renal cell from sepsis-induced injury via miR-181a-5p/PPARα pathway. 相似文献
BackgroundNeuroinflammation is a common therapeutic target for traumatic brain injury (TBI) due to its contribution to delayed secondary cell death and has the potential to occur for years after the initial insult. Previous studies demonstrate that miR-429 is up-regulated in the brain lesions of TBI mice, while its role in regulating neuroinflammation and brain injury remains largely unknown.MethodThe expression of miR-429 in LPS-activated microglia and microglia in TBI model was detected by RT-PCR. The effects of miR-429 inhibitors on LPS-activated microglia in vitro as well as neurological recovery and post-traumatic neuroinflammatory response in TBI model mice were detected in vivo.ResultsLPS and TBI significantly induce the up-expression of miR-429, inflammatory cytokines, MAPK-p38 and phosphorylated NF-κB in microglia, which were all inhibited by miR-429 inhibitors. Meanwhile, miR-429 inhibitors also attenuated the neurological impairment in TBI mice. Bioinformatics analysis showed that miR-429 could target and inhibit the expression of dual specificity protein phosphatase 1 (DUSP1), thus inhibiting the expression of MAPK-p38 and phosphorylated NF-κB.ConclusionmiR-429 plays a pro-inflammatory role in activated microglia by targeting DUSP1 signaling pathway. Inhibiting miR-429 can attenuate the inflammatory response of microglia and TBI-mediated brain damage. 相似文献
Parkinson’s disease (PD) is the second most common neurodegenerative disorder. Neuroinflammation induced by microglia plays an important role in the pathogenesis of PD. Long noncoding RNA GAS5 was showed to have significant effects on regulating inflammatory response. Here, we aim to investigate the effects of GAS5 on the inflammatory response of PD, and the underlying mechanism. An in vivo model of PD was established in C57BL/6 mice by rotenone and an in vitro cell model was conducted on microglia by lipopolysaccharide (LPS). Our results indicated that GAS5 was upregulated in tissues in a mice model of PD and microglia activated by LPS. Gain- and loss- of functional experiments demonstrated that GAS5 promoted the inflammation of microglia in vitro. Besides, the knockdown of GAS5 repressed the PD progression in vivo. Mechanistically, GAS5 positively regulated the NLRP3 expression via competitively sponging miR-223-3p. Overall, our finding illuminates that GAS5 accelerates PD progression through targeting miR-223-3p/NLRP3 axis. 相似文献