Simultaneous ultraviolet-C and near-infrared enhancement in heterogeneous lanthanide nanocrystals.

Lanthanide-doped nanocrystals that simultaneously convert near-infrared (NIR) irradiation into emission of shorter (ultraviolet-C, UVC) and longer wavelengths (NIR) offer many exciting opportunities for application in drug release, photodynamic therapy, deep-tissue bioimaging, and solid-state lasing. However, a formidable challenge is the development of lanthanide-doped nanocrystals with efficient UVC and NIR emissions simultaneously due to their low conversion efficiency. Here, we report a dye-sensitized heterogeneous core-multishell architecture with enhanced UVC emission and NIR emission under 793 nm excitation. This nanocrystal design efficiently suppresses energy trapping induced by interior lattice defects and promotes upconverted UVC emission from Gd3+. Moreover, a significant downshifting emission from Yb3+ at 980 nm was also observed owing to an efficient energy transfer from Nd3+ to Yb3+. Furthermore, by taking advantage of ICG sensitization, we realized a largely enhanced emission from the UVC to NIR spectral region. This study provides a mechanistic understanding of the upconversion and downshifting processes within a heterogeneous architecture while offering exciting opportunities for important biological and energy applications.

LincRNA-EPS alleviates severe acute pancreatitis by suppressing HMGB1-triggered inflammation in pancreatic macrophages.

Acute pancreatitis (AP), an inflammatory disorder of the pancreas with a high hospitalization rate, frequently leads to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). However, therapeutic targets for effective treatment and early intervention of AP are still urgently required to be identified. Here, we have observed that the expression of pancreatic lincRNA-EPS, a long intergenic non-coding RNA, is dynamically changed during both caerulein-induced AP (Cer-AP) and sodium taurocholate-induced severe AP (NaTc-SAP). The expression pattern of lincRNA-EPS is negatively correlated with the typical inflammatory genes such as IL-6, IL-1ß, CXCL1, and CXCL2. Further studies indicate that knockout of lincRNA-EPS aggravates the pathological symptoms of AP including more induction of serum amylase and lipase, severe edema, inflammatory cells infiltration and acinar necrosis in both experimental AP mouse models. Besides these intrapancreatic effects, lincRNA-EPS also protects against tissue damages in the extra-pancreatic organs such as lung, liver, and gut in the NaTc-SAP mouse model. In addition, we have observed more serum pro-inflammatory cytokines TNF-α and IL-6 in the lincRNA-EPS-/- NaTc-SAP mice and more extracellular HMGB1 around injured acinar cells in the pancreas from lincRNA-EPS-/- NaTc-SAP mice, compared with their respective controls. Pharmacological inhibition of NF- κ B activity by BAY11-7082 significantly abolishes the suppressive effect of lincRNA-EPS on TLR4 ligand-induced inflammatory genes in macrophages. Our study has described a protective role of lincRNA-EPS in alleviating AP and SAP, outlined a novel pathway that lincRNA-EPS suppresses HMGB1-NF- κ B-dependent inflammatory response in pancreatic macrophages and provided a potential therapeutic target for SAP.

Microscale Self-Assembly of Upconversion Nanoparticles Driven by Block Copolymer.

Lanthanide-based upconversion nanoparticles can convert low-energy excitation to high-energy emission. The self-assembled upconversion nanoparticles with unique structures have considerable promise in sensors and optical devices due to intriguing properties. However, the assembly of isotropic nanocrystals into anisotropic structures is a fundamental challenge caused by the difficulty in controlling interparticle interactions. Herein, we report a novel approach for the preparation of the chain-like assemblies of upconversion nanoparticles at different scales from nano-scale to micro-scale. The dimension of chain-like assembly can be fine-tuned using various incubation times. Our study observed Y-junction aggregate morphology due to the flexible nature of amphiphilic block copolymer. Furthermore, the prepared nanoparticle assemblies of upconversion nanoparticles with lengths up to several micrometers can serve as novel luminescent nanostructure and offer great opportunities in the fields of optical applications.

Pseudostellaria heterophylla Extract Polysaccharide H-1-2 Suppresses Pancreatic Cancer by Inhibiting Hypoxia-Induced AG2.

We aimed to examine the therapeutic potential of polysaccharide H-1-2, a bioactive component of Pseudostellaria heterophylla, against pancreatic cancer, as well as to demonstrate the underlying molecular mechanisms. Invasion and migration of pancreatic cells treated with H-1-2 were evaluated. A xenograft tumor mouse model was established to assess the effect of H-1-2 on tumor growth. Expression levels of hypoxic inducible factor-1α (HIF1α) and anterior gradient 2 (AGR2) were measured in pancreatic cells after H-1-2 treatment. Luciferase report and chromatin immunoprecipitation assays were conducted to investigate HIF1α regulation on AGR2. AGR2 expression was re-introduced into pancreatic cells to assess the role of AGR2 as a downstream effector of hypoxia after H-1-2 treatment. H-1-2 inhibited invasion and migration of pancreatic cancer cells, repressed xenograft pancreatic tumor growth, and increased survival of mice. H-1-2 repressed AGR2 expression in pancreatic cancer cells through the hypoxia response element (HRE) in its promoter region. Ectopic AGR2 expression partially negated the H-1-2 inhibitory effect on invasion and migration of pancreatic cells and on xenograft pancreatic tumors growth, and it also compromised the H-1-2 promotional effect on survival of mice. We conclude that H-1-2 suppresses pancreatic cancer by inhibiting hypoxia-induced AGR2 expression, supporting further investigation into its efficacy against pancreatic cancer in clinical settings.

Corrigendum: Natural Killer Cell-Derived Exosomal miR-3607-3p Inhibits Pancreatic Cancer Progression by Targeting IL-26.

[This corrects the article DOI: 10.3389/fimmu.2019.02819.].

Association of total cholesterol with severe acute pancreatitis: A U-shaped relationship.

BACKGROUND & AIMS: There is no consensus on relationship between total cholesterol levels and incidence of severe acute pancreatitis (SAP). The aim of this study was to investigate the relation between total cholesterol (TC) and the disease severity of acute pancreatitis. METHODS: We conducted a cross-sectional study on patients with acute pancreatitis between April 2012 and December 2015 in a university hospital. Fasting blood total cholesterol (TC) was assayed within 24 h of admission, as well as 3-5 days, 7-9 days and 13-15 days during hospitalization. Time interval before admission, age, gender, Body Mass Index, hypertension, diabetes mellitus, alcohol consumption, smoking, etiology and albumin were recorded as potential confounding factors. To assess the pattern of relationship of TC and SAP, we used restricted cubic spline analysis with multivariable logistic regression analysis. We also compared total cholesterol concentrations between patients with or without SAP at different time points. RESULTS: 648 patients (median age: 47.5 years; 62.4% man) were enrolled. The incidence of SAP was 10%. A U-shaped association of TC level within 24 h of admission with severity was observed in acute pancreatitis. Patients with low TC levels (<160 mg/dL) and high TC levels (>240 mg/dL) had a significantly higher incidence of SAP and protracted hospital stays when compared to moderate TC levels (160-240 mg/dL). Low total cholesterol levels (OR 2.72; 95 %eCI 1.27-5.83; P = 0.01) and high total cholesterol levels (OR 2.54; 95 %eCI 1.09-5.89; P = 0.03), were still independently associated with development of SAP after adjusting for potential confounding factors. Longitudinal cohort study indicated that patients with SAP had lower total cholesterol concentrations among 3-15 days after admission compared to patients without SAP (P < 0.001). CONCLUSIONS: Both low TC level (<160 mg/dL) and high TC (>240 mg/dL) within 24 h of admission is independently associated with an increased risk of SAP.

DPP4 Inhibitor Attenuates Severe Acute Pancreatitis-Associated Intestinal Inflammation via Nrf2 Signaling.

Severe acute pancreatitis (SAP) is a challenging disease with high morbidity and mortality, often complicated by multiple organ dysfunction syndrome (MODS). The intestine, a major organ involved in MODS, correlates strongly with the evolution of the disease. In this study, we demonstrated that the DPP4 inhibitor, sitagliptin, protects SAP-associated intestinal injury both in vitro and in vivo. These beneficial effects were achieved by suppressing oxidative stress and inflammatory responses. Moreover, in sitagliptin-treated SAP mice, expression of Nrf2 was induced and that of NF-κB was reduced, compared to the control SAP mice. In addition, we used Nrf2-/- mice to test the protective effect of Nrf2 during sitagliptin treatment of SAP; our results indicated that Nrf2-/- mice had greater pancreatic and intestinal injury than wild-type mice. Taken together, high levels of ROS induced by SAP may be inhibited by sitagliptin, possibly by inactivating the Nrf2-NF-κB pathway.

Reply to: Comments on "Nomograms based on inflammatory biomarkers for predicting tumor grade and micro-vascular invasion in stage I/II hepatocellular carcinoma".

We appreciate to receive commentary from Dr Guangtong Deng and Dr Liang Xiao to our article, "Nomograms based on inflammatory biomarkers for predicting tumor grade and micro-vascular invasion in stage I/II hepatocellular carcinoma". First, neutrophil-to-lymphocyte ratio (NLR) and derived NLR (dNLR) are two different parameters. Some studies show that NLR is inconsistent with dNRL in prognostic value through multivariate Cox regression, therefore, it is reasonable that both NLR and dNLR entered into multivariate analysis simultaneously. Second, it is common that articles of predictive nomograms turned continuous variables into categorical variables. The reason is that the categorization of patient clinical variables is beneficial to doctors to make decisions based on the risk level of individual patients in clinical. At last, multicenter validation is quite difficult and we have listed the shortcomings in the limitations of our article. Further validation will need the joint efforts by other institutions.

Lipoxin A4 Ameliorates Acute Pancreatitis-Associated Acute Lung Injury through the Antioxidative and Anti-Inflammatory Effects of the Nrf2 Pathway.

Acute lung injury (ALI) is a critical event involved in the pathophysiological process of acute pancreatitis (AP). Many methods have been widely used for the treatment of AP-ALI, but few are useful during early inflammation. Lipoxin A4 (LXA4), a potent available anti-inflammatory and novel antioxidant mediator, has been extensively studied in AP-ALI, but its underlying mechanism as a protective mediator is not clear. This research was conducted to identify the possible targets and mechanisms involved in the anti-AP-ALI effect of LXA4. First, we confirmed that LXA4 strongly inhibited AP-ALI in mice. Next, using ELISA, PCR, and fluorescence detection to evaluate different parameters, LXA4 was shown to reduce the inflammatory cytokine production induced by AP and block reactive oxygen species (ROS) generation in vivo and in vitro. In addition, TNF-α treatment activated the nuclear factor E2-related factor 2 (Nrf2) signaling pathway and its downstream gene heme oxygenase-1 (HO-1) in human pulmonary microvascular endothelial cells (HPMECs), and LXA4 further promoted their expression. This study also provided evidence that LXA4 phosphorylates Ser40 and triggers its nuclear translocation to activate Nrf2. Moreover, when Nrf2-knockout (Nrf2-/-) mice and cells were used to further assess the effect of the Nrf2/HO-1 pathway, we found that Nrf2 expression knockdown partially eliminated the effect of LXA4 on the reductions in inflammatory factor levels while abrogating the inhibitory effect of LXA4 on the ROS generation stimulated by AP-ALI. Overall, LXA4 attenuated the resolution of AP-induced inflammation and ROS generation to mitigate ALI, perhaps by modulating the Nrf2/HO-1 pathway. These findings have laid a foundation for the treatment of AP-ALI.

The DNA methylation profile of non-coding RNAs improves prognosis prediction for pancreatic adenocarcinoma.

BACKGROUND: Compelling lines of evidence indicate that DNA methylation of non-coding RNAs (ncRNAs) plays critical roles in various tumour progression. In addition, the differential methylation of ncRNAs can predict prognosis of patients. However, little is known about the clear relationship between DNA methylation profile of ncRNAs and the prognosis of pancreatic adenocarcinoma (PAC) patients. METHODS: The data of DNA methylation, RNA-seq, miRNA-seq and clinical features of PAC patients were collected from TCGA database. The DNA methylation profile was obtained using the Infinium HumanMethylation450 BeadChip array. LASSO regression was performed to construct two methylation-based classifiers. The risk score of methylation-based classifiers was calculated for each patient, and the accuracy of the classifiers in predicting overall survival (OS) was examined by ROC curve analysis. In addition, Cox regression models were utilized to assess whether clinical variables and the classifiers were independent prognostic factors for OS. The targets of miRNA and the genes co-expressed with lncRNA were identified with DIANA microT-CDS and the Multi-Experiment Matrix (MEM), respectively. Moreover, DAVID Bioinformatics Resources were applied to analyse the functional enrichment of these targets and co-expressed genes. RESULTS: A total of 4004 CpG sites of miRNA and 11,259 CpG sites of lncRNA were screened. Among these CpG sites, 8 CpG sites of miRNA and 7 CpG sites of lncRNA were found with regression coefficients. By multiplying the sum of methylation degrees of the selected CpGs with these coefficients, two methylation-based classifiers were constructed. The classifiers have shown good performance in predicting the survival rate of PAC patients at varying follow-up times. Interestingly, both of these two classifiers were predominant and independent factors for OS. Furthermore, functional enrichment analysis demonstrated that aberrantly methylated miRNAs and lncRNAs are related to calcium ion transmembrane transport and MAPK, Ras and calcium signalling pathways. CONCLUSION: In the present study, we identified two methylation-based classifiers of ncRNA associated with OS in PAC patients through a comprehensive analysis of miRNA and lncRNA profiles. We are the first group to demonstrate a relationship between the aberrant DNA methylation of ncRNAs and the prognosis of PAC, and this relationship would contribute to individualized PAC therapy.

Downregulation of TNF-α/TNF-R1 Signals by AT-Lipoxin A4 May Be a Significant Mechanism of Attenuation in SAP-Associated Lung Injury.

Our previous studies verified the potent anti-inflammatory effects against severe acute pancreatitis (SAP) of AT-Lipoxin A4 and their analogues. However, the anti-inflammatory effects of AT-Lipoxin A4 on SAP-associated lung injury are not thoroughly known. We used western blot, polymerase chain reaction (PCR), and immunofluorescence to investigate the downregulation of TNF-α signals in cellular and animal models of SAP-associated lung injury following AT-Lipoxin A4 intervention. In vitro, we found that AT-Lipoxin A4 markedly suppressed protein expression in TNF-α signals in human pulmonary microvascular endothelial cell, such as tumor necrosis factor receptor-associated factor 2 (TRAF2), TNF-R1-associated death domain (TRADD), receptor-interacting protein (RIP), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. Moreover, AT-Lipoxin A4 inhibited downstream signals activated by TNF-α, including NF-κB/p65, JNK/MAPK, and ERK/MAPK. In vivo, AT-Lipoxin A4 significantly decreased pathological scores of the pancreas and lungs and the serum levels of IL-6 and TNF-α. Immunofluorescence, western blotting, and real-time PCR assay showed that AT-Lipoxin A4 significantly attenuated the expression of TNF-R1, TRADD, TRAF2, and RIP in the lungs of SAP rats. In addition, the activation of NF-κB was also downregulated by AT-Lipoxin A4 administration as compared with SAP rats. AT-Lipoxin A4 could inhibit the production of proinflammatory mediators and activation of TNF-α downstream signals such as NF-κB and MAPK. Downregulation of TNF-α signals by AT-Lipoxin A4 may be a significant mechanism in the attenuation of SAP-associated lung injury.

Development and validation of a risk prediction score for severe acute pancreatitis.

INTRODUCTION: The available prognostic scoring systems for severe acute pancreatitis (SAP) have limitations that restrict their clinical value. The aim of this study was to develop a simple model (score) that could rapidly identify those at risk for SAP. METHODS: We derived a risk model using a retrospective cohort of 700 patients by logistic regression and bootstrapping methods. The discriminative power of the risk model was assessed by calculating the area under the receiver operating characteristic curves (AUC). The classification and regression tree (CART) analysis was used to create risk categories. The model was internally validated by a tenfold cross-validation and externally validated in a separate prospective cohort of 194 patients. RESULTS: The incidence of SAP was 9.7% in the derivation cohort and 9.3% in the validation cohort. A prognostic score (We denoted it as the SABP score), ranging from 0 to 10, consisting of systemic inflammatory response syndrome, serum albumin, blood urea nitrogen and pleural effusion, was developed by logistic regression and bootstrapping analysis. Patients could be divided into three risk categories according to total SABP score based on CART analysis. The mean probability of developing SAP was 1.9%, 12.8% and 41.6% in patients with low (0-3), moderate (4-6) and high (7-10) SABP score, respectively. The AUCs of prognostic score in tenfold cross-validation was 0.873 and 0.872 in the external validation. CONCLUSION: Our risk prediction score may assist physicians in predicting the development of SAP.

TLR3 Ligand PolyI:C Prevents Acute Pancreatitis Through the Interferon-ß/Interferon-α/ß Receptor Signaling Pathway in a Caerulein-Induced Pancreatitis Mouse Model.

Acute pancreatitis (AP) is a common and devastating inflammatory disorder of the pancreas. However, there are still no effective treatments available for the disease. Therefore, it is important to discover new therapeutic targets and strategies for better treatment and prognosis of AP patients. Toll-like receptor 3 (TLR3) ligand polyI:C is a double-stranded RNA mimic that can be used as an immune stimulant. Our current study indicates that polyI:C exerted excellent anti-inflammatory effects in a caerulein-induced AP mouse model and taurocholate-induced pancreatic acinar cell line injury model. We found that polyI:C triggers type I interferon (IFN) production and downstream IFN-α/ß receptor (IFNAR)-dependent signaling, which play key roles in protecting the pancreas from inflammatory injury. Knockout of IFN-ß and IFNAR in mice abolished the preventive effects of polyI:C on caerulein-induced AP symptoms, which include pancreatic edema, neutrophil infiltration, the accumulation of reactive oxygen species (ROS), and inflammatory gene expression. Treating pancreatic acinar 266-6 cells with an IFNAR inhibitor, which blocks the interaction between type I IFN and IFNAR, diminishes the downregulation of oxidative stress by polyI:C. Additionally, a subsequent transcriptome analysis on the role of polyI:C in treating pancreatitis suggested that chemotaxis of neutrophils and the production of ROS were inhibited by polyI:C in the pancreases damaged by caerulein injection. Thus, polyI:C may act as a type I IFN inducer to alleviate AP, and it has the potential to be a promising therapeutic agent used at the early stages of AP.

Molybdenum disulfide-integrated photonic barcodes for tumor markers screening.

As a new class of two-dimensional (2D) materials, molybdenum disulfide (MoS2) has huge potential in biomedical area; while its applications in multiplex bioassays are still a challenge. Here, we present novel MoS2-integrated silica colloidal crystal barcode (SCCB) for multiplex microRNA (miRNA) screening. MoS2 was adsorbed on SCCBs by electrostatic interaction, and quantum dots (QDs) decorated hairpin probes were coupled on MoS2 by covalent linkage. As the MoS2 could quench the QDs of the hairpin probes, they together formed a molecular beacon (MB) structure before the detection. When used in assays, target miRNA could form a double strand with the probe and made QDs keep away from MoS2 sheets to recovery their fluorescence. Because the released QDs were positively correlated with the concentration of the hybridized nucleic acid, the target miRNAs could be quantified by measuring the fluorescence signal of the QDs on the SCCBs. In addition, by utilizing different MoS2-integrated structural color encoded SCCBs, multiplexed miRNA quantification could also be realized. Based on this strategy, we have demonstrated that several pancreatic cancer-related miRNAs could be selectivity and sensitivity detected with a detection limit of 4.2 ±â€¯0.3 nM. These features make the MoS2-integrated SCCB ideal for many potential applications.

Quantitative proteomics identifies brain acid soluble protein 1 (BASP1) as a prognostic biomarker candidate in pancreatic cancer tissue.

BACKGROUND: Pancreatic cancer is a heterogenous disease with a poor prognosis. This study aimed to discover and validate prognostic tissue biomarkers in pancreatic cancer using a mass spectrometry (MS) based proteomics approach. METHODS: Global protein sequencing of fresh frozen pancreatic cancer and healthy pancreas tissue samples was conducted by MS to discover potential protein biomarkers. Selected candidate proteins were further verified by targeted proteomics using parallel reaction monitoring (PRM). The expression of biomarker candidates was validated by immunohistochemistry in a large tissue microarray (TMA) cohort of 141 patients with resectable pancreatic cancer. Kaplan-Meier and Cox proportional hazard modelling was used to investigate the prognostic utility of candidate protein markers. FINDINGS: In the initial MS-discovery phase, 165 proteins were identified as potential biomarkers. In the subsequent MS-verification phase, a panel of 45 candidate proteins was verified by the development of a PRM assay. Brain acid soluble protein 1 (BASP1) was identified as a new biomarker candidate for pancreatic cancer possessing largely unknown biological and clinical functions and was selected for further analysis. Importantly, bioinformatic analysis indicated that BASP1 interacts with Wilms tumour protein (WT1) in pancreatic cancer. TMA-based immunohistochemistry analysis showed that BASP1 was an independent predictor of prolonged survival (HR 0.468, 95% CI 0.257-0.852, p = .013) and predicted favourable response to adjuvant chemotherapy, whereas WT1 indicated a worsened survival (HR 1.636, 95% CI 1.083-2.473, p = .019) and resistance to chemotherapy. Interaction analysis showed that patients with negative BASP1 and high WT1 expression had the poorest outcome (HR 3.536, 95% CI 1.336-9.362, p = .011). INTERPRETATION: We here describe an MS-based proteomics platform for developing biomarkers for pancreatic cancer. Bioinformatic analysis and clinical data from our study suggest that BASP1 and its putative interaction partner WT1 can be used as biomarkers for predicting outcomes in pancreatic cancer patients.

Hollow Colloid Assembled Photonic Crystal Clusters as Suspension Barcodes for Multiplex Bioassays.

Barcode particles have a demonstrated value for multiplexed high-throughput bioassays. Here, a novel photonic crystal (PhC) barcode is presented that consists of hollow colloidal nanospheres assembled through microfluidic droplet templates. Due to their gas-filled core, the resultant barcode particles not only show increased refractive index contrast, but also remain in suspension by adjusting the overall density of the PhC to match that of a detection solution. In addition, magnetic nanoparticles can be integrated to give the barcodes a magnetically controllable motion ability. The encoding ability of the barcodes is demonstrated in microRNA detection with high specificity and sensitivity, and the excellent features of the barcodes make them potentially very useful for biomedical applications.

Degradation of endogenous proteins and generation of a null-like phenotype in zebrafish using Trim-Away technology.

Trim-Away is a recent technique to rapidly deplete a protein from any cell type. Guided by antibodies, TRIM21 selects proteins for destruction. However, the applicability of this method in model organisms has not been investigated. Here, we show that Trim-Away can degrade proteins in zebrafish embryos. Trim-Away depletes proteins faster than morpholinos, which enables analysis of protein function during early embryogenesis. Furthermore, Trim-Away can be applied to evaluate the role of maternally contributed proteins in zebrafish embryos. Our findings indicate that Trim-Away is a powerful tool to perform functional analysis of proteins during zebrafish development.

Restoration of miRNA-148a in pancreatic cancer reduces invasion and metastasis by inhibiting the Wnt/ß-catenin signaling pathway via downregulating maternally expressed gene-3.

Various microRNAs (miRNA) have been recognized potential novel tumor markers and have a critical role in cancer development and progression. Recently, methylation of miRNA-148a was identified as a crucial biochemical process in the progression of cancer. However, its potential role and in pancreatic cancer as well as the underlying mechanisms have remained largely elusive. The present study investigated the potential antitumor effect of miR-148a as well as its impact on invasion and metastasis in pancreatic cancer. It was found that the expression of miRNA-148a and the potential predictive biomarker maternally expressed gene-3 (MEG-3) were obviously decreased in human pancreatic cancer tissues compared with those in adjacent non-tumorous tissues. Furthermore, miR-148a was found to be downregulated in pancreatic cancer cell lines compared with normal pancreatic cells through promoter methylation. An MTT assay and a clonogenic assay demonstrated that restoration of miRNA-148a inhibited the proliferation and colony formation of pancreatic cancer cells. In addition, miR-148a transduction led to the upregulation of MEG-3 expression and promoted apoptosis of pancreatic cancer cells. Western blot analysis revealed that transduction of miR-148a markedly decreased the expression levels of C-myc, cyclin D1 and ß-catenin in pancreatic cancer cells. Methylation of miR-148a not only decreased the endogenous ß-catenin levels but also inhibited the nuclear translocation of ß-catenin to delay cell cycle progression. Furthermore, ectopic miR-148a methylation inhibited pancreatic cancer cell migration and invasion via causing an upregulation of MEG-3 expression. Most importantly, ectopic overexpression of miR-148a in pancreatic cancer cells inhibited tumor formation in an animal experiment. Taken together, miR-148a methylation is a crucial regulatory process to inhibit the proliferation and invasion of pancreatic cancer cells, and transduction of miR-148a suppressed the proliferation of pancreatic cancer cells through negative regulation of the Wnt/ß-catenin signaling pathway. The findings of the present study suggested that miRNA-148a acts as a tumor suppressor in pancreatic cancer and may contribute to the development of novel treatments for pancreatic cancer.

The signaling pathways that mediate the anti-cancer effects of caloric restriction.

Caloric restriction (CR) has been shown to promote longevity and ameliorate aging-associated diseases, including cancer. Extensive research over recent decades has revealed that CR reduces IGF-1/PI3K/AKT signaling and increases sirtuin signaling. We recently found that CR also enhances ALDOA/DNA-PK/p53 signaling. In the present review, we summarize the molecular mechanisms underlying the modulation of the IGF-1/PI3K/AKT pathway, sirtuin signaling, and the ALDOA/DNA-PK/p53 pathway by CR. We also summarize the evidence concerning the roles of these signaling pathways in carcinogenesis, and discuss how they are regulated by CR. Finally, we discuss the crosstalk between these signaling pathways.

Surgical Treatment and Chemotherapy of Adult Primary Liver Sarcoma: Experiences from a Single Hospital in China.

BACKGROUND: The aim of this study is to improve the preoperative diagnostic accuracy and treatment results by investigating the clinical features and prognosis of primary liver sarcoma (PLS). METHODS: Clinical data, surgical treatments, adjuvant chemotherapy, and prognosis of 17 PLS patients whose diseases were pathologically confirmed were retrospectively analyzed. RESULTS: The main clinical symptoms included epigastric pain in 9 patients, epigastric distention in 7, and loss of appetite in 4; these symptoms were detected during the postoperative follow-up for gastric carcinoma in 1. The resection rate was 64.7% (12/17), including R0 resection in 10 patients and R1 resection in 2, and laparotomy with biopsy in 5. Five patients accepted an adjuvant selective hepatic artery infusion chemotherapy (mitomycin C 16-20 mg+ 5-fluorouracil 5.0 g+ epirubicin 40-50 mg), and 4 accepted adjuvant systemic chemotherapy (vincristin, cisplatin, cyclophosphamide, and adriamycin). All 5 patients with simple laparotomy died within 1 year, and the overall 1-, 3-, and 5-year survival rates for all patients were 58.8% (10/17), 29.4% (5/17) and 11.7% (2/17), respectively, whereas those were 100.0% (10/10), 50.0% (5/10), and 20.0% (2/10) for R0 resected patients respectively. CONCLUSIONS: The diagnosis of PLS is difficult before operation due to its nonspecific manifestations, and the high survival rate can be achieved by radical resection with adjuvant chemotherapy.