Time Course of Gene Expression Profiling in the Liver of Experimental Mice Infected with Echinococcus multilocularis

BACKGROUND: Alveolar echinococcosis (AE) is a severe chronic parasitic disease which behaves like a slow-growing liver cancer. Clinical observations suggest that the parasite, Echinococcus multilocularis (E. multilocularis) influences liver homeostasis and hepatic cell metabolism. However, this has never been analyzed during the time course of infection in the common model of secondary echinococcosis in experimental mice. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression profiles were assessed using DNA microarray analysis, 1, 2, 3 and 6 months after injection of E. multilocularis metacestode in the liver of susceptible mice. Data were collected at different time points to monitor the dynamic behavior of gene expression. 557 differentially expressed genes were identified at one or more time points, including 351 up-regulated and 228 down-regulated genes. Time-course analysis indicated, at the initial stage of E. multilocularis infection (month 1-2), that most of up-regulated pathways were related to immune processes and cell trafficking such as chemokine-, mitogen-activated protein kinase (MAPK) signaling, and down-regulated pathways were related to xenobiotic metabolism; at the middle stage (month 3), MAPK signaling pathway was maintained and peroxisome proliferator-activated receptor (PPAR) signaling pathway emerged; at the late stage (month 6), most of up-regulated pathways were related to PPAR signaling pathway, complement and coagulation cascades, while down-regulated pathways were related to metabolism of xenobiotics by cytochrome P450. Quantitative RT-PCR analysis of a random selection of 19 genes confirmed the reliability of the microarray data. Immunohistochemistry analysis showed that proliferating cell nuclear antigen (PCNA) was increased in the liver of E. multilocularis infected mice from 2 months to 6 months. CONCLUSIONS: E. multilocularis metacestode definitely exerts a deep influence on liver homeostasis, by modifying a number of gene expression and metabolic pathways. It especially promotes hepatic cell proliferation, as evidenced by the increased PCNA constantly found in all the experimental time-points we studied and by an increased gene expression of key metabolic pathways

A valley-filtering switch based on the Stone-Wales defect array in carbon nanotube

We theoretically demonstrate that valley-filtering switch can be realized in a carbon nanotube (CNT) embedded with a series of Stone-Wales defects. It is due to the fact that such a CNT shows two peculiar subbands which span two Dirac valleys without nontrivial dispersion, just like the flat-bottomed subbands of a zigzag-edged graphene nanoribbon. Considering that similar defects have been experimentally patterned in a CNT in a controllable way, this kind of CNT is a promising device prototype for valleytronic applications

Rapid Identification of Benign Gallbladder Diseases Using Serum Surface-Enhanced Raman Spectroscopy Combined with Multivariate Statistical Analysis

In this study, we looked at the viability of utilizing serum to differentiate between gallbladder (GB) stones and GB polyps using Surface-enhanced Raman spectroscopy (SERS), which has the potential to be a quick and accurate means of diagnosing benign GB diseases. Rapid and label-free SERS was used to conduct the tests on 148 serum samples, which included those from 51 patients with GB stones, 25 patients with GB polyps and 72 healthy persons. We used an Ag colloid as a Raman spectrum enhancement substrate. In addition, we employed orthogonal partial least squares discriminant analysis (OPLS-DA) and principal component linear discriminant analysis (PCA-LDA) to compare and diagnose the serum SERS spectra of GB stones and GB polyps. The diagnostic results showed that the sensitivity, specificity, and area under curve (AUC) values of the GB stones and GB polyps based on OPLS-DA algorithm reached 90.2%, 97.2%, 0.995 and 92.0%, 100%, 0.995, respectively. This study demonstrated an accurate and rapid means of combining serum SERS spectra with OPLS-DA to identify GB stones and GB polyps

Upregulated TUBG1 expression is correlated with poor prognosis in hepatocellular carcinoma

Background Hepatocellular carcinoma (HCC) development is a complex pathological process. Tubulin gamma 1 (TUBG1) plays an oncogenic role in several human cancers; however, its functional role in HCC tumorigenesis remains unknown. Methods Herein we first evaluated the gene expression levels of TUBG1 in HCC using data from The Cancer Genome Atlas and Gene Expression Profiling Interactive Analysis databases. We then elucidated the association between TUBG1 gene expression levels and survival rates of patients with HCC. Cell cycle, proliferation, transwell migration, and matrigel invasion assays were used to study the effects of TUBG1 on the malignant phenotypes of HCC cells. Results Based on the data obtained from the aforementioned databases and our in vitro experiments, TUBG1 was found to be overexpressed in HCC and patients with high TUBG1 expression levels showed a remarkably poor overall survival rate. In addition, the expression of TUBG1 significantly promoted the malignant phenotypes of HCC cells in vitro. Gene ontology term enrichment analysis revealed that co-regulated genes were enriched in biological processes mainly involved in chromosome segregation, chromosomal region, and chromatin binding; moreover, Kyoto Encyclopedia of Genes and Genome pathway analysis showed that they were mainly involved in cell cycle, oocyte meiosis, platinum drug resistance, and the p53 signaling pathway. Conclusions We report that TUBG1 is an important oncogene in HCC. It promotes HCC progression and may serve as a potential prognostic biomarker for HCC. Future studies are warranted to unveil molecular biological mechanisms underlying TUBG1 carcinogenesis

Hepatocyte Proliferation/Growth Arrest Balance in the Liver of Mice during E. multilocularis Infection: A Coordinated 3-Stage Course

Background: Alveolar echinococcosis (AE) is characterized by the tumor-like growth of Echinococcus (E.) multilocularis. Very little is known on the influence of helminth parasites which develop in the liver on the proliferation/growth arrest metabolic pathways in the hepatocytes of the infected liver over the various stages of infection. Methodology/Principal Findings: Using Western blot analysis, qPCR and immunohistochemistry, we measured the levels of MAPKs activation, Cyclins, PCNA, Gadd45b, Gadd45c, p53 and p21 expression in the murine AE model, from day 2 to 360 post-infection. Within the early (day 2–60) and middle (day60–180) stages, CyclinB1 and CyclinD1 gene expression increased up to day30 and then returned to control level after day60; Gadd45b, CyclinA and PCNA increased all over the period; ERK1/ 2 was permanently activated. Meanwhile, p53, p21 and Gadd45c gene expression, and caspase 3 activation, gradually increased in a time-dependent manner. In the late stage (day180–360), p53, p21 and Gadd45c gene expression were significantly higher in infected mice; JNK and caspase 3 were activated. TUNEL analysis showed apoptosis of hepatocytes. No significant change in CyclinE, p53 mRNA and p-p38 expression were observed at any time. Conclusions: Our data support the concept of a sequential activation of metabolic pathways which 1) would first favor parasitic, liver and immune cell proliferation and survival, and thus promote metacestode fertility and tolerance by the host, and 2) would then favor liver damage/apoptosis, impairment in protein synthesis and xenobiotic metabolism, as well a

Improved Yield Prediction of Ratoon Rice Using Unmanned Aerial Vehicle-Based Multi-Temporal Feature Method

Pre-harvest yield prediction of ratoon rice is critical for guiding crop interventions in precision agriculture. However, the unique agronomic practice (i.e., varied stubble height treatment) in rice ratooning could lead to inconsistent rice phenology, which had a significant impact on yield prediction of ratoon rice. Multi-temporal unmanned aerial vehicle (UAV)-based remote sensing can likely monitor ratoon rice productivity and reflect maximum yield potential across growing seasons for improving the yield prediction compared with previous methods. Thus, in this study, we explored the performance of combination of agronomic practice information (API) and single-phase, multi-spectral features [vegetation indices (VIs) and texture (Tex) features] in predicting ratoon rice yield, and developed a new UAV-based method to retrieve yield formation process by using multi-temporal features which were effective in improving yield forecasting accuracy of ratoon rice. The results showed that the integrated use of VIs, Tex and API (VIs & Tex + API) improved the accuracy of yield prediction than single-phase UAV imagery-based feature, with the panicle initiation stage being the best period for yield prediction (R2 as 0.732, RMSE as 0.406, RRMSE as 0.101). More importantly, compared with previous multi-temporal UAV-based methods, our proposed multi- temporal method (multi-temporal model VIs & Tex: R2 as 0.795, RMSE as 0.298, RRMSE as 0.072) can increase R2 by 0.020–0.111 and decrease RMSE by 0.020–0.080 in crop yield forecasting. This study provides an effective method for accurate pre-harvest yield prediction of ratoon rice in precision agriculture, which is of great significance to take timely means for ensuring ratoon rice production and food security

Efficacy of Probiotic Supplementation Therapy for <i>Helicobacter pylori</i> Eradication: A Meta-Analysis of Randomized Controlled Trials - Fig 2

<p><b>A</b> risk of bias graph, <b>B</b> risk of bias summary (“+”low risk; “?”, unclear risk; “-”, high risk).</p

Transcriptional profiles of cytokine/chemokine factors of immune cell-homing to the parasitic lesions: a comprehensive one-year course study in the liver of E. multilocularis-infected mice.

Pathogenesis of chronically developing alveolar echinococcosis (AE) is characterized by a continuous, granulomatous, periparasitic infiltration of immune cells surrounding the metacestode of Echinococcus multilocularis (E.multilocularis) in the affected liver. A detailed cytokine and chemokine profile analysis of the periparasitic infiltrate in the liver has, however, not yet been carried out in a comprehensive way all along the whole course of infection in E. multilocularis intermediate hosts. We thus assessed the hepatic gene expression profiles of 18 selected cytokine and chemokine genes using qRT-PCR in the periparasitic immune reaction and the subsequent adjacent, not directly affected, liver tissue of mice from day 2 to day 360 post intra-hepatic injection of metacestode. DNA microarray analysis was also used to get a more complete picture of the transcriptional changes occurring in the liver surrounding the parasitic lesions. Profiles of mRNA expression levels in the hepatic parasitic lesions showed that a mixed Th1/Th2 immune response, characterized by the concomitant presence of IL-12α, IFN-γ and IL-4, was established very early in the development of E. multilocularis. Subsequently, the profile extended to a combined tolerogenic profile associating IL-5, IL-10 and TGF-β. IL-17 was permanently expressed in the liver, mostly in the periparasitic infiltrate; this was confirmed by the increased mRNA expression of both IL-17A and IL-17F from a very early stage, with a subsequent decrease of IL-17A after this first initial rise. All measured chemokines were significantly expressed at a given stage of infection; their expression paralleled that of the corresponding Th1, Th2 or Th17 cytokines. In addition to giving a comprehensive insight in the time course of cytokines and chemokines in E. multilocularis lesion, this study contributes to identify new targets for possible immune therapy to minimize E. multilocularis-related pathology and to complement the only parasitostatic effect of benzimidazoles in AE