Gustafssonnyborg2583

Irreversible pulmonary hypertension (PH) mainly results from vascular remodeling, in which the aberrant growth of pulmonary arterial smooth muscle cells (PASMCs) plays a significant role. Our previous work suggested that KLF5 and HIF1α are closely associated with the pathogenesis of hypoxic PH as they intervene in the growth of PASMCs. MicroRNAs (miRNAs) have been demonstrated to be involved in the control of cell proliferation and apoptosis. In the present study, we detected the expression of six miRNAs connected with KLF5 in hypoxia-exposed rat PH models and PASMCs and then further investigated the role of miR-320-3p in the abnormal proliferation of hypoxic PASMCs and in the progression and treatment outcomes of hypoxia-induced PH. The results indicated that miR-320-3p was downregulated in hypoxia-exposed rat PH models, hypoxia-induced PASMCs and chronic thromboembolic pulmonary hypertension (CTEPH) patients. Moreover, miR-320-3p directly regulated the expression of KLF5 and HIF1α. miR-320-3p mimics inhibited proliferation and migration and promoted apoptosis in hypoxic PASMCs. KLF5 and HIF1α reversed the above effects of miR-320-3p. In conclusion, miR-320-3p plays a certain role in the progression of hypoxic PH via KLF5 and HIF1α and might be a potent therapeutic tool for PH.Our previous study found that tryptase activated atrial fibroblasts, increased collagen synthesis in atrial fibroblasts through protease activated receptor-2 (PAR2) receptors. Isoprenaline datasheet Recent studies showed that cytoskeleton-associated protein 4 (CKAP4) played an important role in ventricular fibroblast activation. The present study aimed to investigate the role of CKAP4 in tryptase-induced atrial fibroblast activation, atrial fibrosis, and molecular regulatory mechanisms. We cultured atrial fibroblasts in vitro, gave cells tryptase stimulation, then overexpressed or silenced PAR2 and CKAP4 genes in the cells. Their effects on atrial fibroblast proliferation, migration, extracellular matrix remodeling (Collagen I and fibronectin) and downstream key molecules (TGF-β1, c-jun and c-fos, JNK, p38) were investigated. The results showed that the expression of CKAP4 was significantly increased by tryptase and further increased by pcDNA3.1-PAR2, but decreased by FALLRY-NH2 and PAR2 siRNA. CKAP4 overexpression significantly increased the cell proliferation, migration and levels of Collagen I and fibronectin, matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels in atrial fibroblasts, while CKAP4 siRNA significantly reduced them. CKAP4 overexpression significantly increased the expression of TGF-β1, c-jun and c-fos, and activated the JNK/p38 pathway, which were suppressed by CKAP4 siRNA. In conclusion, CKAP4 is involved in tryptase-induced phenotypic conversion in atrial fibroblasts through PAR2/p38/JNK pathway, which may provide novel targets in the prevention of atrial fibrosis.

Renal cell carcinoma (RCC) is one of the most common and life-threatening cancers in the world. Accumulating evidence suggest propofol inhibits the initiation and development of cancers. The main focus of the study was to explore the effect of propofol on RCC and its mechanism of action.

In this study, different doses of propofol were used to treat human RCC cell lines i.e., OSRC-2 and SW839. Western blot and trans-well assays were used for the evaluation of RCC cell invasion, proliferation, migration, and transition of epithelial to mesenchymal (EMT). RCC cells following 5 μmol/L propofol treatment for 24 h were applied in the subsequent experiments. Expression of MicroRNAs-363 (miR-363) in cells with or without propofol treatment were analyzed. The expression of Snail1, Vimentin, N-cadherin, and E-cadherin in RCC cells was measured, and then the effect of loss-of-function of miR-363 and gain-of-function of Snail on RCC cells were analyzed. The targeted relationship between miR-363 and Snail1 was investigated using luciferase assay and RIP, RNA pull down.

Propofol reduced the migration, proliferation, invasion and EMT of RCC cells in a dose-dependent way. Propofol elevated miR-363 expression but reduced Snail1 expression, and it reduced Vimentin and N-cadherin but increased E-cadherin expression in RCC cells. miR-363 directly bounds to Snail1. miR-363 inhibition or Snail1 promotion reversed propofol-inhibited malignant behaviors of RCC cells.

Our study found that propofol could inhibit invasion, migration, proliferation and EMT of RCC cells by promoting miR-363 expression and suppressing Snail1 expression.

Our study found that propofol could inhibit invasion, migration, proliferation and EMT of RCC cells by promoting miR-363 expression and suppressing Snail1 expression.

The family of MAGE genes is well known due to the majority of MAGE genes expressing specifically in tumor tissues while restrictedly in normal tissues. MAGE-D4 is one of the MAGE family and considered as a promising target for glioma immunotherapy because of its overexpression in glioma and restricted expression in normal tissues. Whereas the mechanism of MAGE-D4 heterogeneous expression in glioma has not yet been elucidated. In this study, the transcriptional regulation mechanism of MAGE-D4 in glioma is focused from the perspectives of promoter methylation and SP1.

Dual-luciferase reporter assay was performed to identify the core promoter of MAGE-D4 gene. Mass spectrometry was applied to quantify the methylation status of MAGE-D4 promoter in 50 glioma and 9 normal brain tissues. The influence of methylation and SP1 on MAGE-D4 transcriptional activity was evaluated by dual-luciferase reporter assay, qRT-PCR, western blot and ChIP-qPCR. Decitabine, an epigenetic drug, was used to treat the glioma cells. Th-activation of MAGE-D4 promoter by demethylation and SP1 in glioma cell lines.

These findings indicate that the synergies of promoter hypomethylation and SP1 up-regulated MAGE-D4 transcription in glioma, which implies a potential approach to resolve the heterogeneous expression of MAGE-D4 in order to establish foundation for the MAGE-D4 based glioma therapy.

These findings indicate that the synergies of promoter hypomethylation and SP1 up-regulated MAGE-D4 transcription in glioma, which implies a potential approach to resolve the heterogeneous expression of MAGE-D4 in order to establish foundation for the MAGE-D4 based glioma therapy.

This research was designed to probe into the regulatory mechanism of long non-coding RNA (LncRNA) differentiation antagonizing non-protein coding RNA (DANCR) in potential applications and molecular mechanisms of prostate carcinoma (PC).

The DANCR and miR-214-5p levels in PC tissues and cell lines were tested via real-time PCR, and those of transforming growth factor-β (TGF-β) signaling pathway related proteins were evaluated via Western Blot (WB). Cell proliferation, migration, apoptosis and the regulatory relationship between target genes were assessed via MTT method, scratch test, flow cytometry, dual-luciferase report, RNA co-immunoprecipitation and RNA pull-down test, respectively.

DANCR was up-regulated in PC patients' serum and cell lines, while miR-214-5p was opposite, showing negative correlation. Besides, DANCR was significantly correlated with PSA, Gleason score and T stage in PC patients. The area under the curve (AUC) of DANCR and miR-214-5p for diagnosing PC was not less than 0.850, while the AUC for predicting poor prognosis was more than 0.800. Cox analysis results also revealed that the two might be prognostic indicators of PC patients. We found that DANCR high levels or miR-214-5p low levels were related to PC patients' poor prognosis. Up-regulating DANCR or down-regulating miR-214-5p could promote PC cells' malignant proliferation and migration, prevent apoptosis, and activate TGF-β signaling pathway, while reverse treatment of DANCR or miR-214-5p can reverse the above results. DANCR regulates miR-214-5p in a targeted manner, and DANCR over-expression can reduce the cancer inhibitory effect of miR-214-5p on PC cells.

DANCR-miR-214-5p-TGF-β axis regulatory network plays a key regulatory part in PC progression. It may provide new strategies for the screening and treatment of patients.

DANCR-miR-214-5p-TGF-β axis regulatory network plays a key regulatory part in PC progression. It may provide new strategies for the screening and treatment of patients.

To investigate the role of rehabilitation training and TLR4/MyD88 signaling pathway on neuronal apoptosis in mice with cerebral ischemic stroke.

Mice were randomized into six groups, which were normal group (healthy mice, n=20), control group (sham surgery, n=20), model group (middle cerebral artery occlusion (MCAO) model, n=20), training (MCAO model, continuous rehabilitation training for 4 weeks, n=20), TAK-242 group (MCAO model, TL R4 inhibitor TAK-242, n=20), and TAK-242 + Training group (MCAO model, TLR4 inhibitor TAK-242 + rehabilitation training, n=20).

Neurobehavioral assessment was performed, and cerebral infarction area of mice was detected by triphenyl tetrazolium chloride staining. Compared with the normal group, no significant differences in all indicators were found in the control group (all P>0.05), while the other groups had higher neurological function scores, cerebral infarction area, neuronal apoptosis rate, increased expressions of TLR4, MyD88, Bax, NF-κB, TNF-α, Caspase-3, IL-1βA and decreased mRNA and protein expressions of Bcl-2 (all P<0.05).

Rehabilitation training can effectively reduce the apoptosis of hippocampal neurons in mice with ischemic stroke by inhibiting the TLR4/MyD88 signaling pathway.

Rehabilitation training can effectively reduce the apoptosis of hippocampal neurons in mice with ischemic stroke by inhibiting the TLR4/MyD88 signaling pathway.Coronary heart disease (CHD) is one of the most vital reasons for death and disability all over the world. miRNA, as a plasma index, is quite valuable for disease screening and prognosis prediction in CHD. Mining the molecular mechanism behind miRNA is also helpful for us to find molecular therapeutic strategies. In this research, we found that the expression of plasma miR-30c-5p in CHD patients was obviously lower than that in the control group (CG), which had a high differential value for CHD. We also discovered that miR-30c-5p was obviously correlated with clinical characteristics of CHD patients such as age, NYHA grade, smoking history, hypertension, hyperlipidemia, etc. In prognosis analysis, the miR-30c-5p expression in patients with poor prognosis was dramatically lower than that in those with good one, and the AUC for predicting poor prognosis of CHD was not lower than 0.850. In addition, we also induced myocardial ischemia/reperfusion (I/R) injury model of H9C2 cells through hypoxia/reoxygenation, and found that H9C2 cells also had abnormally down-regulated miR-30c-5p and up-regulated BCL2-like 11 (BCL2L11). Up-regulating miR-30c-5p or down-regulating BCL2L11 were helpful to improve proliferation and apoptosis of I/R injury model. Mechanically, BCL2L11 was also negatively regulated by miR-30c-5p, and up-regulating the former could cancel the in vitro protective effect of up-regulating the latter on H9C2 cell I/R injury model. In vivo research, up-regulating miR-30c-5p or down-regulating BCL2L11 can improve myocardial injury, histopathological changes and apoptosis in rat I/R model.