Long non-coding RNAs (lncRNAs) are essential factors that regulate tumor development and metastasis via diverse molecular mechanisms in a broad type of cancers. However, the pathological roles of ...lncRNAs in gallbladder carcinoma (GBC) remain largely unknown. Here we discovered a novel lncRNA termed lncRNA Highly expressed in GBC (lncRNA-HGBC) which was upregulated in GBC tissue and aimed to investigate its role and regulatory mechanism in the development and progression of GBC.
The expression level of lncRNA-HGBC in GBC tissue and different cell lines was determined by quantitative real-time PCR. The full length of lncRNA-HGBC was obtained by 5' and 3' rapid amplification of the cDNA ends (RACE). Cellular localization of lncRNA-HGBC was detected by fluorescence in situ hybridization (FISH) assays and subcellular fractionation assay. In vitro and in vivo assays were preformed to explore the biological effects of lncRNA-HGBC in GBC cells. RNA pull-down assay, mass spectrometry, and RNA immunoprecipitation (RIP) assay were used to identify lncRNA-HGBC-interacting proteins. Dual luciferase reporter assays, AGO2-RIP, and MS2-RIP assays were performed to verify the interaction between lncRNA-HGBC and miR-502-3p.
We found that lncRNA-HGBC was upregulated in GBC and its upregulation could predict poor survival. Overexpression or knockdown of lncRNA-HGBC in GBC cell lines resulted in increased or decreased, respectively, cell proliferation and invasion in vitro and in xenografted tumors. LncRNA-HGBC specifically bound to RNA binding protein Hu Antigen R (HuR) that in turn stabilized lncRNA-HGBC. LncRNA-HGBC functioned as a competitive endogenous RNA to bind to miR-502-3p that inhibits target gene SET. Overexpression, knockdown or mutation of lncRNA-HGBC altered the inhibitory effects of miR-502-3p on SET expression and downstream activation of AKT. Clinically, lncRNA-HGBC expression was negatively correlated with miR-502-3p, but positively correlated with SET and HuR in GBC tissue.
Our study demonstrates that lncRNA-HGBC promotes GBC metastasis via activation of the miR-502-3p-SET-AKT cascade, pointing to lncRNA-HGBC as a new prognostic predictor and a therapeutic target.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Baicalein, a widely used Chinese herbal medicine, has multiple pharmacological activities. However, the precise mechanisms of the anti-proliferation and anti-metastatic effects of baicalein on ...gallbladder cancer (GBC) remain poorly understood. Therefore, the aim of this study was to assess the anti-proliferation and anti-metastatic effects of baicalein and the related mechanism(s) on GBC. In the present study, we found that treatment with baicalein induced a significant inhibitory effect on proliferation and promoted apoptosis in GBC-SD and SGC996 cells, two widely used gallbladder cancer cell lines. Additionally, treatment with baicalein inhibited the metastasis of GBC cells. Moreover, we demonstrated for the first time that baicalein inhibited GBC cell growth and metastasis via down-regulation of the expression level of Zinc finger protein X-linked (ZFX). In conclusion, our studies suggest that baicalein may be a potential phytochemical flavonoid for therapeutics of GBC and ZFX may serve as a molecular marker or predictive target for GBC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Long noncoding RNAs (lncRNAs) play roles in the development and progression of many cancers; however, the contributions of lncRNAs to human gallbladder cancer (GBC) remain largely unknown. In this ...study, we identify a group of differentially expressed lncRNAs in human GBC tissues, including prognosis-associated gallbladder cancer lncRNA (lncRNA-PAGBC), which we find to be an independent prognostic marker in GBC. Functional analysis indicates that lncRNA-PAGBC promotes tumour growth and metastasis of GBC cells. More importantly, as a competitive endogenous RNA (ceRNA), lncRNA-PAGBC competitively binds to the tumour suppressive microRNAs miR-133b and miR-511. This competitive role of lncRNA-PAGBC is required for its ability to promote tumour growth and metastasis and to activate the AKT/mTOR pathway. Moreover, lncRNA-PAGBC interacts with polyadenylate binding protein cytoplasmic 1 (PABPC1) and is stabilized by this interaction. This work provides novel insight on the molecular pathogenesis of GBC.
Synopsis
Long noncoding RNAs play roles in the development and progression of many cancers. In this study the lncRNA PAGBC is identified as promoting tumorigenesis in human gallbladder cancer by competitive binding to the tumour suppressive microRNAs miR-133b and miR-511.
LncRNA-PAGBC is up-regulated in GBC and increased levels associate with poor prognosis.
LncRNA-PAGBC promotes tumour growth and metastasis, and activates AKT/mTOR signaling by competitively binding to mirR-133b and mirR-511.
LncRNA-PAGBC interacts with and is stabilized by the polyadenylate binding protein PABPC1.
Graphical Abstract
Long noncoding RNAs play roles in the development and progression of many cancers. In this study the lncRNA PAGBC is identified as promoting tumorigenesis in human gallbladder cancer by competitive binding to the tumour suppressive microRNAs miR-133b and miR-511.
The development height of a gas conducting fracture zone (GFZ) in the gob overlying strata is crucial to the gas drainage and safe production of a coal mine. In order to address the issues of ...excessive gas concentration and uncertain GFZ height in No. 7435 Face overlying strata of Kongzhuang Coal Mine, China, the caving characteristics of overlying strata were explored using both physical experiments on similar materials and numerical simulations of Particle Flow Code (PFC) software and verified each other. The relationship of cracks development to porosity changing characteristics was introduced to quantitatively determine the height of the local GFZ. The quantified GFZ heights were compared with those measured using the in-situ drilling flow method. The results showed that 1) PFC software could accurately simulate the overlying strata caving behaviors, thus saving manpower, materials and financial resources needed for related physical experiments, and 2) the temporospatial distribution characteristics of porosity could be used to forecast GFZ height, and are of significant importance for determination of GFZ. Overall, the conclusions are of engineering significance for accurate arrangement of boreholes for gas drainage and reduction of mine gas disasters.
•Experiments using similar materials proved that the particle flow numerical simulation is reliable.•The development height of the mining-affected fracture zone was quantitatively studied based on porosity distribution.•The porosity-divided gas-conducting fracture zone is verified by the water leakage through boreholes method•Quantified porosity distribution is of significance for flow field research.
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long non-coding RNA (lncRNA), is associated with metastasis and is an independent prognostic factor for lung cancer. Recent studies ...have demonstrated that MALAT1 plays an important role in other malignancies. However, little is known about the role of MALAT1 in gallbladder carcinoma (GBC), which is the most common cancer of the biliary tract and has an extremely poor prognosis. In this study, we focused on the expression, biological functions and mechanism of MALAT1 in GBC and found that MALAT1 was significantly upregulated in GBC tissues compared with corresponding non-cancerous tissues. Knockdown of MALAT1 in GBC cell lines using lentivirus-mediated RNA interference significantly inhibited the proliferation and metastasis of the GBC cells both in vitro and in vivo. Furthermore, ERK/MAPK pathway was found to be inactivated in the GBC cell lines after MALAT1 knockdown. These results indicated that MALAT1 might serve as an oncogenic lncRNA that promotes proliferation and metastasis of GBC and activates the ERK/MAPK pathway
Background
Three‐dimensional visualization preoperative evaluation (3D‐VPE) and enhanced recovery after surgery (ERAS) have been suggested to improve outcomes of cancer surgery in patients, yet ...little is known regarding their clinical benefit in patients with gallbladder cancer (GBC). We hypothesized that the combination of 3D‐VPE and ERAS would improve the outcome of patients undergoing surgery for GBC.
Objective
This study aimed to determine if 3D‐VPE and ERAS can improve the outcomes and overall survival in patients with GBC, establishing a novel patient management strategy for GBC.
Methods
A total of 227 patients with GBC were recruited and divided into two groups: those who received traditional treatment between January 2000 and December 2010 (n = 86; the control group) and those who underwent 3D‐VPE and ERAS between January 2011 and December 2017 (n = 141). Univariate and multivariate analyses were employed to assess the relationship among disease stages, lymph node invasion, and cell differentiation between the two groups. Cox regression analysis was used to investigate patient survival in these groups.
Results
Patients who underwent 3D‐VPE and ERAS showed a significantly higher R0 resection rate (67.4% vs. 20.9%, p < 0.001) and dissected lymph node number (26.6 ± 12.6 vs. 16.3 ± 7.6 p < 0.001) compared to the control group. The median survival was 27.4 months, and the 1‐ and 3‐year survival rates were 84.4% and 29.8%, respectively, in patients who received combined management; in the control cohort, the median survival was 12.7 months, and the 1‐ and 3‐year survival rates were 53.5% and 15.1%, respectively. In addition, some postoperative complications and risk factors were diminished relative to the traditionally treated patients.
Conclusion
The implementation of 3D‐VPE and ERAS can significantly improve the prognosis and outcomes of patients with GBC and should be considered for wide use in clinical practice.
This is a retrospective study of patients with gallbladder cancer (GBC) treated at our institution over the course of 17 years. We show that three‐dimensional visualization preoperative evaluation and enhanced recovery after surgery can significantly improve prognosis and outcomes of patients with GBC and should be considered for wide use in clinical practice.
Staphylococcus aureus
is a bacterial pathogen that causes food poisoning, various infections, and sepsis. Effective strategies and new drugs are needed to control
S. aureus
associated infections due ...to the emergence and rapid dissemination of antibiotic resistance. In the present study, the antibacterial activity, potential mode of action, and applications of flavonoids from licorice were investigated. Here, we showed that glabrol, licochalcone A, licochalcone C, and licochalcone E displayed high efficiency against methicillin-resistant
Staphylococcus aureus
(MRSA). Glabrol, licochalcone A, licochalcone C, and licochalcone E exhibited low cytotoxicity without hemolytic activity based on safety evaluation. Glabrol displayed rapid bactericidal activity with low levels of resistance development
in vitro
. Meanwhile, glabrol rapidly increased bacterial membrane permeability and dissipated the proton move force. Furthermore, we found that peptidoglycan, phosphatidylglycerol, and cardiolipin inhibited the antibacterial activity of glabrol. Molecular docking showed that glabrol binds to phosphatidylglycerol and cardiolipin through the formation of hydrogen bonds. Lastly, glabrol showed antibacterial activity against MRSA in both
in vivo
and
in vitro
models. Altogether, these results suggest that glabrol is a promising lead compound for the design of membrane-active antibacterial agents against MRSA and can be used as a disinfectant candidate as well.
Glabrol isolated from licorice rapidly kill MRSA
via
the disruption of the membrane permeability and the proton motive force.
Gallbladder cancer (GBC) is the most common malignant tumour of the biliary track system. Angiogenesis plays a pivotal role in the development and progression of malignant tumours. miR-143-3p acts as ...a tumour suppressor in various cancers. Their role in GBC is however less well defined. Here we show that the expression levels of miR-143-3p were decreased in human GBC tissues compared with the non-tumour adjacent tissue (NAT) counterparts and were closely associated with overall survival. We discovered that miR-143-3p was a novel inhibitor of tumour growth and angiogenesis in vivo and in vitro. Our antibody array, ELISA and PLGF rescue analyses indicated that PLGF played an essential role in the antiangiogenic effect of miR-143-3p. Furthermore, we used miRNA target-prediction software and dual-luciferase assays to confirm that integrin α6 (ITGA6) acted as a direct target of miR-143-3p. Our ELISA and western blot analyses confirmed that the expression of PLGF was decreased via the ITGA6/PI3K/AKT pathway. In conclusion, miR-143-3p suppresses tumour angiogenesis and growth of GBC through the ITGA6/PI3K/AKT/PLGF pathways and may be a novel molecular therapeutic target for GBC.
Coagulation and fibrinolysis activation is frequently observed in cancer patients, and the tumors in these cases are thought to be associated with a higher risk of invasion, metastasis, and worse ...long-term outcome. The objective of this study was to elucidate the prognostic significance of blood coagulation tests and various clinicopathological characteristics in patients with gallbladder cancer (GBC) after surgical resection.
We retrospectively reviewed the medical records of 115 patients with histologically confirmed GBC who underwent surgical resection in our department. The prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), international normalized ratio (INR), fibrinogen levels, and platelet counts were measured pretreatment at the time of diagnosis. The predictive value of fibrinogen levels for tumor staging was evaluated using a receiver operating characteristic (ROC) curve analysis. Correlations between the preoperative hyperfibrinogenemia and clinicopathological characteristics were analyzed, and univariate and multivariate survival analyses were performed to identify the factors associated with overall survival (OS). Cancer cell migration and invasion in vitro were examined to investigate the function of fibrinogen in GBC cell migration.
The plasma levels for all coagulation tests, with the exception of INR, were significantly different between the GBC patients and control patients (p < 0.001). Hyperfibrinogenemia (>402 mg/dL) was associated with poorly differentiated tumors, advanced tumor invasion, lymphatic metastasis, and advanced tumor stage (p < 0.001), and had a statistically significant adverse effect on survival (p = 0.001). In the multivariate analysis, hyperfibrinogenemia (p = 0.031) was independently associated with worse OS, tumor stage (p = 0.016), margin status (p < 0.001), and lymphatic metastasis (p = 0.035). Moreover, cell migration and invasion in vitro were significantly enhanced by fibrinogen.
Preoperative plasma fibrinogen levels was associated with tumor progression and may be an independent marker of poor prognosis in GBC patients. Furthermore, fibrinogen may contribute to cell migration by inducing epithelial-mesenchymal transition.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tantalum and its alloys are regarded as equipment construction materials for processing aggressive acidic media due to their excellent properties. In this study, the influence of severe rolling (90%) ...on the dissolution rate of a cold-rolled Ta-4%W sheet in different directions was investigated during immersion testing and the corresponding mechanism was discussed. The results show that the dissolution rate of the cold-rolled sample is significantly lower than that of the undeformed sample. The corrosion resistance followed the sequence of “initial” < “90%-ND” < “90%-RD” < “90%-TD”, while the strength is in positive correlation with the corrosion resistance. Severe rolling promotes grain subdivision accompanied by long geometrically necessary boundaries and short incidental dislocation boundaries on two scales in the cold-rolled sample. The volume elements enclosed by geometrically necessary boundaries form preferential crystallographic orientations. Such preferential crystallographic orientations can greatly weaken the electrochemical process caused by adjacent volume elements, resulting in greatly reduced corrosion rates in the severely deformed sample. The unexpected finding provides a new idea for tailoring the structures of tantalum alloys to improve both their strength and corrosion resistance.
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