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
Single-chamber atrial pacing is effective in the management of sinus node dysfunction, subject to the uncertainty of long-term atrioventricular conduction. Despite the accepted observation that many patients with sinus node dysfunction also have atrioventricular conduction disease, data do not exist on the development of atrioventricular block in those patients with permanent single-chamber atrial pacing. Of 70 patients who received single-chamber atrial pacing from 1967 to 1982 (mean duration of pacing was 33 months), only two patients of 58 (3.4%) of those with sinus node dysfunction developed atrioventricular (AV) block—after 14 months in one patient and after 23 months of successful atrial pacing in the other. None of the 12 patients paced for tachyarrhythmia management developed AV block. Of the 70 patients, 37 had assessment of AV conduction by incremental atrial pacing at the time of implant and 20 patients underwent atrial pacing on the basis of surface ECG and clinical judgment. Electrophysiologic studies were conducted only in those patients being paced for control of supraventricular arrhythmias. Only 5 of the 70 patients required conversion to ventricular pacing for technical difficulties; three of these conversions occurred in the early 1970's before the advent of atrial tined or J leads; one was for irreparable lead fracture and only one occurred in a patient with a newer design atrial lead. In conclusion, progression to AV block in patients with permanent atrial pacing is uncommon; formal electrophysiologic studies are necessary mainly in patients with supraventricular arrhythmias; and in the majority of patients, AV conduction can be assessed at the time of implant. Continued improvement in atrial leads should make atrial pacing even more successful. 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
BACKGROUND: Lymphangioleiomyomatosis (LAM), a multisystem disease occurring primarily in women, is characterized by cystic lung destruction, and kidney and lymphatic tumors, caused by the proliferation of abnormal-appearing cells (ie, LAM cells) with a smooth muscle cell phenotype that express melanoma antigens and are capable of metastasizing. Estrogen receptors are present in LAM cells, and this finding, along with reports of disease progression during pregnancy or following exogenous estrogen administration, suggest the involvement of estrogens in the pathogenesis of LAM. Consequently, antiestrogen therapies have been employed in treatment. The goal of this prospective study was to evaluate the efficacy of triptorelin, a gonadotrophin-releasing hormone analogue, in 11 premenopausal women with LAM. METHODS: Patients were evaluated at baseline and every 3 to 6 months thereafter, for a total of 36 months. Hormonal assays, pulmonary function tests, 6-min walk tests, high-resolution CT scans of the chest, and bone mineral density studies were performed. RESULTS: Gonadal suppression was achieved in all patients. Overall, a significant decline in lung function was observed; two patients underwent lung transplantation 1 year after study enrollment, and another patient was lost to follow-up. Treatment with triptorelin was associated with a decline in bone mineral density. CONCLUSIONS: Triptorelin appears not to prevent a decline in lung function in patients with LAM. Its use, however, may be associated with the loss of bone mineral density. 相似文献
Comprehensive cardiac rehabilitation is not for every patient, but rather for those who require more than the services of a physician and a nurse. The services which eventually are required may be provided simply in some cases by paramedical persons and in the more complicated cases by an experienced multidisciplinary team. The main evaluative expertise of cardiac rehabilitation specialists is the functional evaluation of the patient—that is, the physical, psychological, social, and vocational functioning by a variety of specialized techniques. The major therapeutic recommendation is usually endurance-building exercise training for secondary prevention. The educational and supportive aspects of the rehabilitation process may make the difference between non-limiting impairment and disability. 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