The neuromedin B receptor (Nmbr) is an important physiological regulator of spontaneous activities and stress responses through different cascades as well as its autocrine and paracrine effects. Previous studies have revealed that neuromedin B (Nmb) and its receptor signal via the Rela (also known as p65)/Il6 pathway in a mouse model of pregnancy. This study investigated the mechanism of Nmbr signaling via the Rela/p65-Il6 pathway and regulation of the concentration of intracellular free calcium ([Ca(2+)](i)) during the onset of labor in primary mouse myometrial cell cultures isolated from mice in term labor. Data demonstrated Nmbr agonist-mediated upregulation of the DNA binding activity of Rela/p65, Il6 expression, and [Ca(2+)](i) in a concentration-dependent manner. Furthermore, a significant correlation was observed between DNA binding activity of Rela/p65 and Il6 expression. Moreover, this up-regulation was blocked by Nmbr and Rela/p65 knockdown, achieved by RNA interference (RNAi) technology. No significant differences were identified in the inhibition of Il6 expression as a result of Nmbr or Rela/p65 knockdown. However, significant differences were observed between the [Ca(2+)](i) in Rela/p65-specific group and that in the Nmbr-specific small interfering RNA (siRNA)-treated groups. These data demonstrated that the Nmb/Nmbr interaction in pregnant myometrial primary cells in vitro predominantly influenced uterine activity through regulation of Il6 expression via the Rela/p65 pathway, although the effects of Nmbr on [Ca(2+)](i) involved several pathways that remain to be elucidated.
is reported to exhibit cancer-promoting activity in various types of cancer. It has been previously demonstrated that miR-21 is overexpressed in bladder tumor tissue compared with normal mucosa. However, the functional mechanism of miR-21 in bladder cancer remains largely unknown. Thus, the current study aimed to determine the roles of miR-21 in autophagy and the malignant development of bladder cancer in T24 cells. Upregulation or downregulation of miR-21 was achieved following the transfection of miR-21 mimic or miR-21 inhibitor. An MTT assay was additionally performed to measure cell growth. Wound healing and transwell invasion assays were used to detect cell migration and invasion. The apoptotic potential and cell cycle were examined via flow cytometry and reverse transcription-quantitative PCR was performed to evaluate the expression of phosphatase and tensin homolog (PTEN), beclin 1, microtubule-associated protein l light chain 3B (LC3-II), cyclin D1, caspase-3, E-cadherin, matrix metallopeptidase-9 (MMP-9) and vimentin. The results revealed that the proliferation, migration and invasion of T24 cells was greatly increased in the miR-21 mimic group, while apoptosis was greatly inhibited. Additionally, T24 cells treated with miR-21 mimic exhibited G1-phase arrest. In the miR-21 mimic group, the expression of PTEN, beclin 1, LC3-II, caspase-3 and E-cadherin were decreased, while the expression of cyclin D1, MMP-9 and vimentin were increased. Opposite effects were observed in the miR-21 inhibitor group. The data of the current study may indicate that miR-21 overexpression inhibited autophagy and promoted the proliferation, migration, invasion and epithelial to mesenchymal transition of bladder cancer T24 cells. The results may further elucidate the molecular mechanism of miR-21 in the development of bladder cancer. Materials and methodsCell line and culture. The human bladder cancer cell line, T24, was obtained from the Cell Bank of Type Culture Collection of the Chinese Academy of Sciences. Cells were cultured in
Objectives: Placentae from patients with preeclampsia have increased susceptibility to necroptosis and phosphoglycerate mutase 5 (PGAM5) plays a role in many necrosis pathways. We determined whether PGAM5 promotes necroptosis of trophoblast cells and the underlying mechanisms in this study. Methods:The injury model was established by treating JEG3 cells with hypoxia for 24 h. The functional measurements were assessed by the cell counting kit-8, propidium iodide (PI)/Annexin V staining, JC-1 staining and firefly luciferase ATP assay. The expression of proteins in human placentae and JEG3 cells was measured Western blot.PGAM5 was knocked down to study its role in hypoxia-induced necroptosis. Results:The placentae from patients with preeclampsia showed up-regulation of PGAM5 and decreased levels of p-Drp1-S637, accompanied by increased necroptosisrelevant proteins expression. The expression of PGAM5 in JEG3 cells was up-regulated under hypoxia, which promoted dephosphorylation of Drp1 at Serine 637 residue, mitochondrial dysfunction (elevated ROS level and reduced mitochondrial membrane potential and ATP content) and cellular necroptosis (increased PI + /Annexin V + cells and decreased cell viability), accompanied by increased expression of necroptosisrelevant proteins; knockdown of PGAM5 attenuated these phenomena. Conclusions: Our results indicate that PGAM5 can promote necroptosis in trophoblast cells through, at least in part, activation of Drp1. It may be used as a new therapeutic target to prevent trophoblast dysfunction in preeclampsia.
Purpose: To investigate the risk factors associated with adverse outcomes in patients with residual stones after percutaneous nephrolithotomy (PCNL) and to establish a nomogram to predict the probability of adverse outcomes based on these risk factors. Methods: We conducted a retrospective review of 233 patients who underwent PCNL for upper urinary tract calculi and had postoperative residual stones. The patients were divided into two groups according to whether adverse outcomes occurred, and the risk factors for adverse outcomes were explored by univariate and multivariate analyses. Finally, we created a nomogram for predicting the risk of adverse outcomes in patients with residual stones after PCNL. Results: In this study, adverse outcomes occurred in 125 (53.6%) patients. Multivariate logistic regression analysis indicated that the independent risk factors for adverse outcomes were the diameter of the postoperative residual stones (P < 0.001), a positive urine culture (P = 0.022), and previous stone surgery (P = 0.004). The above independent risk factors were used as variables to construct the nomogram. The nomogram model was internally validated. The calculated concordance index was 0.772. The Hosmer– Lemeshow goodness-of-fit test was performed (P > 0.05). The area under the ROC curve of this model was 0.772. Conclusions: Larger diameter of residual stones, positive urine culture, and previous stone surgery were significant predictors associated with adverse outcomes in patients with residual stones after PCNL. Our nomogram could help to assess the risk of adverse outcomes quickly and effectively in patients with residual stones after PCNL
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