The Lncrna-TUG1/EZH2 Axis Promotes Pancreatic Cancer Cell Proliferation, Migration and EMT Phenotype Formation Through Sponging Mir-382

Background/Aims: Pancreatic carcinoma (PC) is the one of the most common and malignant cancers worldwide. LncRNA taurine upregulated gene 1 (TUG1) was initially identified as a transcript upregulated by taurine, and the abnormal expression of TUG1 has been reported in many cancers. However, the biological role and molecular mechanism of TUG1 in PC still needs further investigation. Methods: Quantitative real-time PCR (qRT-PCR) was performed to measure the expression of TUG1 in PC cell lines and tissues. MTT and colony formation assays were used to measure the effect of TUG1 on cell proliferation. A wound healing assay, transwell assay and western blot assay were employed to determine the effect of TUG1 on cell migration and the epithelial mesenchymal transition (EMT) phenotype. RNA-binding protein immunoprecipitation (RIP) and a biotin-avidin pulldown system were performed to confirm the interaction between miR-328 and TUG1. A gene expression array analysis using clinical samples and RT-qPCR suggested that enhancer of zeste homolog 2 (EZH2) was a target of miR-382 in PC. Results: In this study, we reported that TUG1 was overexpressed in PC tissues and cell lines, and high expression of TUG1 predicted poor prognosis. Further experiments revealed that overexpressed TUG1 promoted cell proliferation, migration and contributed to EMT formation, whereas silenced TUG1 led to opposing results. Additionally, luciferase reporter assays, an RIP assay and an RNA-pulldown assay demonstrated that TUG1 could competitively sponge miR-382 and thereby regulate EZH2. Conclusion: Collectively, these findings revealed that TUG1 functions as an oncogenic lncRNA that promotes tumor progression, at least partially, by functioning as an endogenous ‘sponge’ and competing for miR-382 binding to the miRNA target EZH2

Nanostructured Ternary Metal Tungstate-Based Photocatalysts for Environmental Purification and Solar Water Splitting: A Review

Abstract Visible-light-responsive ternary metal tungstate (MWO4) photocatalysts are being increasingly investigated for energy conversion and environmental purification applications owing to their striking features, including low cost, eco-friendliness, and high stability under acidic and oxidative conditions. However, rapid recombination of photoinduced electron–hole pairs and a narrow light response range to the solar spectrum lead to low photocatalytic activity of MWO4-based materials, thus significantly hampering their wide usage in practice. To enable their widespread practical usage, significant efforts have been devoted, by developing new concepts and innovative strategies. In this review, we aim to provide an integrated overview of the fundamentals and recent progress of MWO4-based photocatalysts. Furthermore, different strategies, including morphological control, surface modification, heteroatom doping, and heterojunction fabrication, which are employed to promote the photocatalytic activities of MWO4-based materials, are systematically summarized and discussed. Finally, existing challenges and a future perspective are also provided to shed light on the development of highly efficient MWO4-based photocatalysts

Development and Evaluation of Nomograms to Predict the Cancer-Specific Mortality and Overall Mortality of Patients with Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common type among primary liver cancers (PLC). With its poor prognosis and survival rate, it is necessary for HCC patients to have a long-term follow-up. We believe that there are currently no relevant reports or literature about nomograms for predicting the cancer-specific mortality of HCC patients. Therefore, the primary goal of this study was to develop and evaluate nomograms to predict cancer-specific mortality and overall mortality. Data of 45,158 cases of HCC patients were collected from the Surveillance, Epidemiology, and End Results (SEER) program database between 2004 and 2013, which were then utilized to develop the nomograms. Finally, the performance of the nomograms was evaluated by the concordance index (C-index) and the area under the time-dependent receiver operating characteristic (ROC) curve (td-AUC). The categories selected to develop a nomogram for predicting cancer-specific mortality included marriage, insurance, radiotherapy, surgery, distant metastasis, lymphatic metastasis, tumor size, grade, sex, and the American Joint Committee on Cancer (AJCC) stage; while the marriage, radiotherapy, surgery, AJCC stage, grade, race, sex, and age were selected to develop a nomogram for predicting overall mortality. The C-indices for predicted 1-, 3-, and 5-year cancer-specific mortality were 0.792, 0.776, and 0.774; the AUC values for 1-, 3-, and 5-year cancer-specific mortality were 0.830, 0.830, and 0.830. The C-indices for predicted 1-, 3-, and 5-year overall mortality were 0.770, 0.755, and 0.752; AUC values for predicted 1-, 3-, and 5-year overall mortality were 0.820, 0.820, and 0.830. The results showed that the nomograms possessed good agreement compared with the observed outcomes. It could provide clinicians with a personalized predicted risk of death information to evaluate the potential changes of the disease-specific condition so that clinicians can adjust therapy options when combined with the actual condition of the patient, which is beneficial to patients

Antitumor efficacy of α-solanine against pancreatic cancer in vitro and in vivo.

α-solanine, a steroidal glycoalkaloid in potato, was found to have proliferation-inhibiting and apoptosis-promoting effect on multiple cancer cells, such as clone, liver, melanoma cancer cells. However, the antitumor efficacy of α-solanine on pancreatic cancer has not been fully evaluated. In this study, we inquired into the anti-carcinogenic effect of α-solanine against human pancreatic cancer cells. In the present study, we investigated the anti-carcinogenic effect of α-solanine against human pancreatic cancer cells. In vitro, α-solanine inhibited proliferation of PANC-1, sw1990, MIA PaCa-2 cells in a dose-dependent manner, as well as cell migration and invasion with atoxic doses. The expression of MMP-2/9, extracellular inducer of matrix metalloproteinase (EMMPRIN), CD44, eNOS and E-cadherin were suppressed by α-solanine in PANC-1 cells. Moreover, significantly decreased vascular endothelial growth factor (VEGF) expression and tube formation of endothelial cells were discerned following α-solanine treatment. Suppressed phosphorylation of Akt, mTOR, and Stat3, and strengthen phosphorylation of β-catenin was found, along with markedly decreased tran-nuclear of NF-κB, β-catenin and TCF-1. Following the administration of α-solanine (6 µg/g for 2 weeks) in xenograft model, tumor volume and weight were decreased by 61% and 43% (p<0.05) respectively, showing decreased MMP-2/9, PCNA and VEGF expression. In conclusion, α-solanine showed beneficial effects on pancreatic cancer in vitro and in vivo, which may via suppressing the pathway proliferation, angiogenesis and metastasis

The rat pancreatic body tail as a source of a novel extracellular matrix scaffold for endocrine pancreas bioengineering

Abstract Background Regenerative medicine and tissue engineering are promising approaches for organ transplantation. Extracellular matrix (ECM) based scaffolds obtained through the decellularization of natural organs have become the preferred platform for organ bioengineering. In the field of pancreas bioengineering, acellular scaffolds from different animals approximate the biochemical, spatial and vascular relationships of the native extracellular matrix and have been proven to be a good platform for recellularization and in vitro culture. However, artificial endocrine pancreases based on these whole pancreatic scaffolds have a critical flaw, specifically their difficult in vivo transplantation, and connecting their vessels to the recipient is a major limitation in the development of pancreatic tissue engineering. In this study, we focus on preparing a novel acellular extracellular matrix scaffold derived from the rat pancreatic body tail (pan-body-tail ECM scaffold). Results Several analyses confirmed that our protocol effectively removes cellular material while preserving ECM proteins and the native vascular tree. DNA quantification demonstrated an obvious reduction of DNA compared with that of the natural organ (from 931.9 ± 267.8 to 11.7 ± 3.6 ng/mg, P  0.05). After transplanted with the recellularized pancreas, fasting glucose levels declined to 9.08 ± 2.4 mmol/l within 2 h of the operation, and 8 h later, they had decreased to 4.7 ± 1.8 mmol/l (P < 0.05). Conclusions The current study describes a novel pancreatic ECM scaffold prepared from the rat pancreatic body tail via perfusion through the left gastric artery. We further showed the pioneering possibility of in vivo circulation-connected transplantation of a recellularized pancreas based on this novel scaffold. By providing such a promising pancreatic ECM scaffold, the present study might represent a key improvement and have a positive impact on endocrine pancreas bioengineering

Recent Advances in Chitosan-Based Metal Nanocomposites for Wound Healing Applications

Chitosan (CS) has been extensively studied as a natural polymer, in the field of wound repair, due to its useful properties, which include a lack of toxicity and stimulation, excellent biological affinity, degradability, and promotion of collagen deposition. However, inferior mechanical strength and moderate antibacterial properties are the drawbacks restricting its further clinical application. Many researchers have adopted the use of nanotechnology, in particular metallic nanoparticles (MNPs), in order to improve the mechanical strength and specific antibacterial properties of chitosan composites, with promising results. Furthermore, chitosan naturally functions as a reducing agent for MNPs, which can also reduce cytotoxicity. Thus, CS, in combination with MNPs, exhibits antibacterial activity, excellent mechanical strength, and anti-inflammatory properties, and it has great potential to accelerate the process of wound healing. This review discusses the current use of CS and MNPs in wound healing and emphasises the synergy and the advantages for various applications in wound healing

Lipoxin A4 attenuation of endothelial inflammation response mimicking pancreatitis-induced lung injury

Lipoxins (LXs) and their analogues are known to display potent anti-inflammatory actions. Previously, we reported that lipoxin A4 (LXA4) possessed powerful anti-inflammatory properties in acute pancreatitis in rats and that it may ameliorate the concomitant acute lung injury by reducing cytokine generation and inhibiting neutrophil activation. Considering that the vascular endothelium plays an important role during adherence, migration and activation of leukocytes, the present study was designed to investigate the effects of LXA4 on the inflammatory response induced by tumor necrosis factor a (TNF-alpha) in human pulmonary microvascular endothelial cells (HPMECs) and explore the potential mechanisms involved in these processes. We found that LXA4 markedly down-regulated the expression of monocyte chemotactic protein-1 (MCP-1), E-selectin, and interleukin-6 (IL-6) mRNA, as well as intercellular adhesion molecule-1 (ICAM-1) in TNF-alpha-exposed HPMECs. Moreover, LXA4 inhibited the phosphorylation and nuclear translocation of nuclear factor-kappa B/p65 (NF-kappa B/p65) and phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) in HPMECs following TNF-alpha stimulation. Heme oxygenase-1 (HO-1), a cytoprotective enzyme, was up-regulated by LXA4 in both non- and TNF-alpha-stimulated HPMECs. In conclusion, the protective effects of LXA4 to ALI may be executed through inhibition inflammation pathways of NF-kappa B and p38 MAPK and up-regulation of cytoprotective HO-1