Study on Differences in the Pathology, T Cell Subsets and Gene Expression in Susceptible and Non-Susceptible Hosts Infected with Schistosoma japonicum

More than 40 kinds of mammals in China are known to be naturally infected with Schistosoma japonicum (S. japonicum); Microtus fortis (M. fortis), a species of vole, is the only mammal in which the schistosomes cannot mature or cause significant pathogenic changes. In the current study, we compared the differences in pathology by Hematoxylin-eosin staining and in changes in the T cell subsets with flow cytometry as well as gene expression using genome oligonucleotide microarrays in the lung and liver, before challenge and 10 days post-infection with schistosomes in a S. japonicum-susceptible mouse model of infection, a non-susceptible rat model and the non-permissive host, M. fortis. The results demonstrated that S. japonicum promoted a more intensive immune response and more pathological lesions in M. fortis and rats than in mice. Hematoxylin-eosin staining revealed that the immune effector cells involved were mainly eosinophilic granulocytes supplemented with heterophilic granulocytes and macrophages. The analysis of splenic T cell subsets showed that CD4+ T cell subsets and the CD4+/CD8+ ratio were increased, while the CD8+ T cell subsets decreased remarkably in rats; whereas the CD8+ T cell subsets were increased, but the CD4+/CD8+ ratio was decreased significantly in mice. The analysis of the pattern of gene expression suggested that some immune-associated genes and apoptosis-inducing genes up-regulated, while some development-associated genes were down-regulated in the infected M. fortis compared to the uninfected controls; the three different hosts have different response mechanisms to schistosome infection. The results of this study will be helpful for identifying the key molecules in the immune response to S. japonicum in M. fortis and for understanding more about the underlying mechanism of the response, as well as for elucidating the interaction between S. japonicum and its hosts

Identification of immune-related genes contributing to the development of glioblastoma using weighted gene co-expression network analysis

Background: The tumor microenvironment (TME) of human glioblastoma (GBM) exhibits considerable immune cell infiltration, and such cell types have been shown to be widely involved in the development of GBM. Here, weighted correlation network analysis (WGCNA) was performed on publicly available datasets to identify immune-related molecules that may contribute to the progression of GBM and thus be exploited as potential therapeutic targets. Methods: WGCNA was used to identify highly correlated gene clusters in Chinese Glioma Genome Atlas glioma dataset. Immune-related genes in significant modules were subsequently validated in the Cancer Genome Atlas (TCGA) and Rembrandt databases, and impact on GBM development was examined in migration and vascular mimicry assays in vitro and in an orthotopic xenograft model (GL261 luciferase-GFP cells) in mice. Results: WGCNA yielded 14 significant modules, one of which (black) contained genes involved in immune response and extracellular matrix formation. The intersection of these genes with a GO immune-related gene set yielded 47 immune-related genes, five of which exhibited increased expression and association with worse prognosis in GBM. One of these genes, TREM1, was highly expressed in areas of pseudopalisading cells around necrosis and associated with other proteins induced in angiogenesis/hypoxia. In macrophages induced from THP1 cells, TREM1 expression levels were increased under hypoxic conditions and associated with markers of macrophage M2 polarization. TREM1 siRNA knockdown in induced macrophages reduced their ability to promote migration and vascular mimicry in GBM cells in vitro, and treatment of mice with LP-17 peptide, which blocks TREM1, inhibited growth of GL261 orthotopic xenografts. Finally, blocking the cytokine receptor for CSF1 in induced macrophages also impeded their potential to promote tumor migration and vascular mimicry in GBM cells. Conclusions: Our results demonstrated that TREM1 could be used as a novel immunotherapy target for glioma patients.publishedVersio

Decaying Hidden Dark Matter in Warped Compactification

The recent PAMELA and ATIC/Fermi/HESS experiments have observed an excess of electrons and positrons, but not anti-protons, in the high energy cosmic rays. To explain this result, we construct a decaying hidden dark matter model in string theory compactification that incorporates the following two ingredients, the hidden dark matter scenario in warped compactification and the phenomenological proposal of hidden light particles that decay to the Standard Model. In this model, on higher dimensional warped branes, various warped Kaluza-Klein particles and the zero-mode of gauge field play roles of the hidden dark matter or mediators to the Standard Model.Comment: 15 pages; v4, several clarifications added, update on Fermi/HESS result

Loss of COPZ1 induces NCOA4 mediated autophagy and ferroptosis in glioblastoma cell lines

Dysregulated iron metabolism is a hallmark of many cancers, including glioblastoma (GBM). However, its role in tumor progression remains unclear. Herein, we identified coatomer protein complex subunit zeta 1 (COPZ1) as a therapeutic target candidate which significantly dysregulated iron metabolism in GBM cells. Overexpression of COPZ1 was associated with increasing tumor grade and poor prognosis in glioma patients based on analysis of expression data from the publicly available database The Cancer Genome Atlas (P < 0.001). Protein levels of COPZ1 were significantly increased in GBM compared to non-neoplastic brain tissue samples in immunohistochemistry and western blot analysis. SiRNA knockdown of COPZ1 suppressed proliferation of U87MG, U251 and P3#GBM in vitro. Stable expression of a COPZ1 shRNA construct in U87MG inhibited tumor growth in vivo by ~60% relative to controls at day 21 after implantation (P < 0.001). Kaplan–Meier analysis of the survival data demonstrated that the overall survival of tumor bearing animals increased from 20.8 days (control) to 27.8 days (knockdown, P < 0.05). COPZ1 knockdown also led to the increase in nuclear receptor coactivator 4 (NCOA4), resulting in the degradation of ferritin, and a subsequent increase in the intracellular levels of ferrous iron and ultimately ferroptosis. These data demonstrate that COPZ1 is a critical mediator in iron metabolism. The COPZ1/NCOA4/FTH1 axis is therefore a novel therapeutic target for the treatment of human GBM.publishedVersio

Microsurgical and tractographic anatomical study of insular and transsylvian transinsular approach

This study is to define the operative anatomy of the insula with emphasis on the transsylvian transinsular approach. The anatomy was studied in 15 brain specimens, among five were dissected by use of fiber dissection technique; diffusion tensor imaging of 10 healthy volunteers was obtained with a 1.5-T MR system. The temporal stem consists mainly of the uncinate fasciculus, inferior occipitofrontal fasciculus, Meyer’s loop of the optic radiation and anterior commissure. The transinsular approach requires an incision of the inferior limiting sulcus. In this procedure, the fibers of the temporal stem can be interrupted to various degrees. The fiber dissection technique is a very relevant and reliable method for neurosurgeons to study the details of brain anatomic features. The DTI fiber tracking technique can identify the fiber tracts of the temporal stem. Moreover, it will also help further functional study of human insula

A Novel Autosomal Dominant Inclusion Body Myopathy Linked to 7q22.1-31.1

We describe a novel autosomal dominant hereditary inclusion body myopathy (HIBM) that clinically mimics limb girdle muscular dystrophy in a Chinese family. We performed a detailed clinical assessment of 36 individuals spanning four generations. The age of onset ranged from the 30s to the 50s. Hip girdle, neck flexion and axial muscle weakness were involved at an early stage. This disease progressed slowly, and a shoulder girdle weakness appeared later in the disease course. Muscle biopsies showed necrotic, regenerating, and rimmed vacuolated fibers as well as congophilic inclusions in some of the fibers. Electron micrograph revealed cytoplasmic inclusions of 15–21 nm filaments. A genomewide scan and haplotype analyses were performed using an Illumina Linkage-12 DNA Analysis Kit (average spacing 0.58 cM), which traced the disease to a new locus on chromosome 7q22.1–31.1 with a maximum multi-point LOD score of 3.65. The critical locus for this unique disorder, which is currently referred to as hereditary inclusion body myopathy 4 (HIBM4), spans 8.78 Mb and contains 65 genes. This localization raises the possibility that one of the genes clustered within this region may be involved in this disorder

A genetic study and meta-analysis of the genetic predisposition of prostate cancer in a Chinese population.

Prostate cancer predisposition has been extensively investigated in European populations, but there have been few studies of other ethnic groups. To investigate prostate cancer susceptibility in the under-investigated Chinese population, we performed single-nucleotide polymorphism (SNP) array analysis on a cohort of Chinese cases and controls and then meta-analysis with data from the existing Chinese prostate cancer genome-wide association study (GWAS). Genotyping 211,155 SNPs in 495 cases and 640 controls of Chinese ancestry identified several new suggestive Chinese prostate cancer predisposition loci. However, none of them reached genome-wide significance level either by meta-analysis or replication study. The meta-analysis with the Chinese GWAS data revealed that four 8q24 loci are the main contributors to Chinese prostate cancer risk and the risk alleles from three of them exist at much higher frequencies in Chinese than European populations. We also found that several predisposition loci reported in Western populations have different effect on Chinese men. Therefore, this first extensive single-nucleotide polymorphism study of Chinese prostate cancer in comparison with European population indicates that four loci on 8q24 contribute to a great risk of prostate cancer in a considerable large proportion of Chinese men. Based on those four loci, the top 10% of the population have six- or two-fold prostate cancer risk compared with men of the bottom 10% or median risk respectively, which may facilitate the design of prostate cancer genetic risk screening and prevention in Chinese men. These findings also provide additional insights into the etiology and pathogenesis of prostate cancer.This work was conducted on behalf of the CHIPGECS and The PRACTICAL consortia (see Supplementary Consortia). We acknowledge the contribution of doctors, nurses and postgraduate research students at the CHIPGENCS sample collecting centers. We thank Orchid and Rosetrees for funding support. This work was also supported by National Natural Science foundation of China for funding support to H Zhang (Grant No: 30671793 and 81072377), N Feng (Grant No: 81272831), X Zhang (Grant No: 30572139, 30872924 and 81072095), S Zhao (Grant No: 81072092 and 81328017), Y Yu (Grant No: 81172448) and Program for New Century Excellent Talents in University from Department of Education of China (NCET-08-0223) and the National High Technology Research and Development Program of China (863 Program 2012AA021101) to X Zhang.This is the final version of the article. It first appeared from Impact Journals via http://dx.doi.org/10.18632/oncotarget.725

Aggregation-Induced Emission (AIE), Life and Health

Light has profoundly impacted modern medicine and healthcare, with numerous luminescent agents and imaging techniques currently being used to assess health and treat diseases. As an emerging concept in luminescence, aggregation-induced emission (AIE) has shown great potential in biological applications due to its advantages in terms of brightness, biocompatibility, photostability, and positive correlation with concentration. This review provides a comprehensive summary of AIE luminogens applied in imaging of biological structure and dynamic physiological processes, disease diagnosis and treatment, and detection and monitoring of specific analytes, followed by representative works. Discussions on critical issues and perspectives on future directions are also included. This review aims to stimulate the interest of researchers from different fields, including chemistry, biology, materials science, medicine, etc., thus promoting the development of AIE in the fields of life and health