Tubeimoside-1 (TBMS1) is a natural compound isolated from tubeimoside, which has been widely used as a traditional Chinese herbal medicine. The purpose of the present study is to investigate the ...anti-tumor effect and the underling mechanism of TBMS1 on glioma cancer cells.
The MTT assay was performed to evaluate the effect of TBMS1 on glioma cell proliferation. The fluorescent microscopy and flow cytometry analysis were performed to evaluate the effect of TBMS1 on glioma cell apoptosis. The Western blot analysis was used to evaluate the protein change.
TBMS1 inhibited glioma cancer cell proliferation in a dose- and time-dependent manner. Fluorescent microscopy and flow cytometry analysis demonstrated that TBMS1 induced glioma cell apoptosis in a concentration-dependent manner. Western blotting showed that TBMS1 induced apoptosis by increasing the expression of Bax and downregulating the level of Bcl-2. Furthermore, we found that TBMS1 induced apoptosis by increasing the concentration of reactive oxygen species through the release of Cytochrome C and activation of Caspase-3.
These findings indicate that TBMS1 may be developed as a possible therapeutic agent for the management of glioma.
Astrocytoma is one of the most common primary central nervous system tumors and has both high mortality and a poor 5-year survival rate. MicroRNAs (miRNAs) play important roles in carcinogenesis by ...acting on multiple signaling pathways. Although we have demonstrated that miR-137 is downregulated in astrocytoma tissues, the role of miR-137 in astrocytoma still remains unknown. In the present study, we aimed to investigate the function of miR-137 and its possible target genes in astrocytoma. miR-137 was significantly downregulated in astrocytoma tissues, and its expression level was inversely correlated with the clinical stage. Restoring miR-137 was able to dramatically inhibit cell proliferation, migration, and invasion and enhance apoptosis in vitro, whereas silencing its expression inhibited these processes. By overexpressing or inhibiting miR-137 in cancer cells, we experimentally confirmed that miR-137 directly recognized the 3′-UTR (3′-untranslated region) of the RASGRF1 (Ras protein-specific guanine nucleotide-releasing factor 1) transcript and regulated RASGRF1 expression. Furthermore, an inverse correlation was observed between miR-137 levels and RASGRF1 protein levels, but not mRNA levels, in astrocytoma samples. The silencing of RASGRF1 resulted in similar effects to miR-137 restoration in cancer cells. Finally, overexpression of RASGRF1 rescued the inhibitory effects of miR-137. Taken together, our results indicate that miR-137 acts as a tumor suppressor in astrocytoma by targeting RASGRF1. These findings suggest that miR-137 may serve as a novel therapeutic target in astrocytoma treatment.
Long noncoding RNAs (lncRNAs) are pervasively transcribed and play a key role in tumorigenesis. The aim of the study was to determine the lncRNA expression profile in astrocytomas and to assess its ...potential clinical value. We performed a three-step analysis to establish the lncRNA profile for astrocytoma: a) the lncRNA expression was examined on 3 astrocytomas as well as 3 NATs (normal adjacent tissues) using the lncRNA microarray; b) the top-hits were validated in 40 astrocytomas (WHO grade II-IV) by quantitative real time-PCR (qRT-PCR); c) the hits with significant differences were re-evaluated using qRT-PCR in 90 astrocytomas. Finally, 7 lncRNAs were found to have a significantly different expression profile in astrocytoma samples compared to the NAT samples. Unsupervised clustering analysis further revealed the potential of the 7-lncRNA profile to differentiate between tumors and NAT samples. The upregulation of ENST00000545440 and NR_002809 was associated with advanced clinical stages of astrocytoma. Using Kaplan-Meier survival analysis, we showed that the low expression of BC002811 or XLOC_010967, or the high expression of NR_002809 was significantly associated with poor patient survival. Moreover, Cox proportional hazard regression analysis revealed that this prognostic impact was independent of other clinicopathological factors. Our results indicate that the lncRNA profile may be a potential prognostic biomarker for the prediction of post-surgical outcomes.
Astrocytomas are common malignant intracranial tumors that comprise the majority of adult primary central nervous system tumors. MicroRNAs (miRNAs) are small, non-coding RNAs (20-24 nucleotides) that ...post-transcriptionally modulate gene expression by negatively regulating the stability or translational efficiency of their target mRNAs. In our previous studies, we found that the downregulation of miR-106a-5p in astrocytomas is associated with poor prognosis. However, its specific gene target(s) and underlying functional mechanism(s) in astrocytomas remain unclear. In this study, we used mRNA microarray experiments to measure global mRNA expression in the presence of increased or decreased miR-106a-5p levels. We then performed bioinformatics analysis based on multiple target prediction algorithms to obtain candidate target genes that were further validated by computational predictions, western blot analysis, quantitative real-time PCR, and the luciferase reporter assay. Fas-activated serine/threonine kinase (FASTK) was identified as a direct target of miR-106a-5p. In human astrocytomas, miR-106a-5p is downregulated and negatively associated with clinical staging, whereas FASTK is upregulated and positively associated with advanced clinical stages, at both the protein and mRNA levels. Furthermore, Kaplan-Meier analysis revealed that the reduced expression of miR-106a-5p or the increased expression of FASTK is significantly associated with poor survival outcome. These results further supported the finding that FASTK is a direct target gene of miR-106a-5p. Next, we explored the function of miR-106a-5p and FASTK during astrocytoma progression. Through gain-of-function and loss-of-function studies, we demonstrated that miR-106a-5p can significantly inhibit cell proliferation and migration and can promote cell apoptosis in vitro. The knockdown of FASTK induced similar effects on astrocytoma cells as those induced by the overexpression of miR-106a-5p. These observations suggest that miR-106a-5p functions as a tumor suppressor during the development of astrocytomas by targeting FASTK.
The study of rock fracturing is a fundamental research topic in rock mechanics and engineering. In this paper, based on complete stress–strain curves obtained under TTC and the corresponding AE and ...strain energy results, the mechanical properties and fracturing process of Beishan granite are studied. A representative test result (σ2 = 75 MPa, σ3 = 20 MPa) is selected to analyse and illustrate the three-dimensional fracturing process of the Beishan granite. The results show that the variations in the characteristics of the brittle fracture behaviour, AE and strain energy of Beishan granite change with σ2 or σ3 following certain relationships, and the mechanisms driving these various relationships are very different. The AE and strain energy characteristics of Beishan granite are also quite different among the five fracturing evolution stages. The variations in the increments of AE count, AE event and total elastic strain energy per unit time (ΔSc/Δt, ΔSe/Δt and ΔUe/Δt) are studied at different times and under different stresses during rock failure. The rock fracturing evolution can be illustrated through the variation in these parameters, providing deep insight. This research provides a perspective for studying deep underground fracture-forming processes, such as earthquakes, tunnel sudden failure, spalling, splitting and rockburst.
A multilayer complex network model with multiple and directed weights is firstly proposed in this brief. Then, under suitable coupling protocols in virtue of time lags, the successive lag ...synchronization (SLS) among layers can be realized, which is a new type of dynamical behavior for complex networks. Especially, when there is no time lag among layers, SLS becomes complete synchronization. This model can bridge the gap between complete synchronization for reducible coupling matrices, cluster synchronization, classical SLS, etc. Sufficient conditions for SLS are obtained by the re-arranging variables' order technique, which is recently developed for networks with multiple weights. Finally, numerical simulations are given to verify our results.
In view of a previous study of the intermediate principal stress effect at a limited
σ
2
range, a series of true triaxial tests, covering a full range of intermediate principal stresses that vary ...from the generalized triaxial compression stress state (
σ
2
=
σ
3
) to the generalized triaxial tensile stress state (
σ
1
=
σ
2
), was carried out on sandstone and granite samples. The experimental results revealed that the deformation, failure strength and failure mode have a significant dependence on the stress state. As an effect of the intermediate principal stress on crack evolution, the deformation difference known as stress-induced deformation anisotropy occurred and should be considered when developing the mechanical model. Moreover, a post-peak deformation with a step-shaped stress drop is observed and illustrates that there will be a multi-stage bearing capacity after the rock failure. The peak strength is non-symmetrical with the increasing
σ
2
and is closely related to the Lode angle. Based on the final fracture surface and SEM analysis under true triaxial compression, three failure modes and failure zones, including tension failure, shear failure and mixed failure, are delineated and discussed. Combining the failure mode and the strength under true triaxial compression, it is found that the strength variation exhibited a close relationship to the failure mechanism.
A true triaxial apparatus (TTA) was designed and fabricated at Northeastern University, Shenyang, China, by modifying the original Mogi type testing apparatus to emulate three-dimensional stress ...paths in deep mining and tunneling excavations. Such an apparatus can be used to investigate deformation and brittle failure behaviors of hard rocks as well as the cause of rockbursts. The novel TTA can capture the post-peak behavior of a 50 × 50 × 100 mm
3
specimen. Technical improvements such as a considerable increase of the stiffness of the loading frames were implemented to deal with difficulties in TTA testing. The accuracy of the volume change measurement was improved and a combined pneumatic and hydraulic technique was applied to create a “floating” vertical loading frame. The end friction effect and the loading gap effect were evaluated using a series of tests. Repeatability tests, brittle failure tests in a loading stress path and an unloading stress path (unloading of
σ
3
) were carried out on granite specimens to verify the performance of the TTA. The test results show that the apparatus achieves its original design goal.
Kong et al discuss the study on crack initiation and damage stress in sandstone under true triaxial compression. Rock masses in deep underground engineering are characterized by a complex geological ...environment and mechanical properties with frequent hazards such as excavation-induced spalling, rock burst and collapse. These failure behaviors result in a significant challenge for the construction of underground engineering and the prediction of abrupt hazards. It is also found that the crack initiation stress and crack damage stress have a relationship with the stress state in which the intermediate principal stress must be taken into consideration.
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