RIP3 blockade prevents immune-mediated hepatitis through a myeloid-derived suppressor cell dependent mechanism

Autoimmune hepatitis (AIH) is an immune-mediated chronic inflammatory liver disease, and its pathogenesis is not fully understood. Our previous study discovered that receptor interacting protein kinase 3 (RIP3) is correlated with serum transaminase levels in AIH patients. However, its role and underlying mechanism in AIH are poorly understood. Here, we detected the increased expression and activation of RIP3 in livers of patients and animal models with AIH. The inhibition of RIP3 kinase by GSK872 prevented concanavalin A (ConA)-induced immune-mediated hepatitis (IMH) by reduced hepatic proinflammatory cytokines and immune cells including Th17 cells and macrophages. Further experiments revealed that RIP3 inhibition resulted in an increase in CD11b⁺Gr1⁺ myeloid-derived suppressor cells (MDSCs) with immunoregulatory properties in the liver, spleen, and peripheral blood. Moreover, the depletion of Gr-1⁺ MDSCs abrogated the protective effect and immune suppression function of GSK872 in ConA-induced IMH. Altogether, our data demonstrate that RIP3 blockade prevents ConA-induced IMH through promoting MDSCs infiltration. Inhibition of RIP3 kinase may be a novel therapeutic avenue for AIH treatment.     

Prediction of the Mechanism of Action of Fusaricidin on Bacillus subtilis

Long-term use of antibiotics has engendered a large number of resistant pathogens, which pose a serious threat to human health. Here, we investigated the mechanism of fusaricidin antibacterial activity toward Bacillus subtilis and characterized the pathways responsible for drug resistance. We found that σ^w, an extracytoplasmic function sigma factor, plays an important role in the resistance to fusaricidins during the initial 5 minutes of drug addition. Approximately 18 genes were induced more than 3-fold, of which 66.7% are known to be regulated by σ^w. Over the following 3 h, fusaricidins induced 194 genes more than three-fold, and most were associated with classes of antibiotic-responsive stimulons. Moreover, the fusaricidin treatment increased the catabolism of fatty and amino acids but strongly repressed glucose decomposition and gluconeogenesis. In summary, our data provide insight into the mechanism of fusaricidin activity, on which we based our suggested strategies for the development of novel antibiotic agents.     

Extraskeletal myxoid chondrosarcoma in the lung: asymptomatic lung mass with severe anemia

ABSTRACT: Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft-tissue sarcoma, which primarily occurs deep in the extremities, especially in skeletal muscle, or tendon. EMC of the pleura has been described, however, no case of primary EMC arising from lung has been previously reported. We describe herein, a 51-year-old Asian female initially manifested with signs of severe anemia who presented with a lung mass unrelated to pleura that was morphologically typical EMC, with strong immunoreactivity for vimentin and NSE. Two weeks after resection, the anemia was cured. The patient continued with follow-up, without sign of abnormality 32 months after operation.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2882199847396682.     

Molecular characterization and expression analysis of a complement component 3 in the sea cucumber (Apostichopus japonicus)

The complement system has been discovered in invertebrates and vertebrates, and plays a crucial role in the innate defense against common pathogens. As a central component in the complement system, complement component 3 (C3) is an intermediary between innate and adaptive immune system. In this study, a new isoform of C3 in the sea cucumber Apostichopus japonicus, termed AjC3-2 was identified. Its open reading frame (ORF) is 5085?bp and encodes for 1695 amino acids with a putative signal peptide of 20 amino acid residues. The mature protein molecular weight of AjC3-2 was 187.72?kDa. It has a conserved thioester site and a linker R(689)RRR(692) where AjC3-2 is splitted into β and α chain during posttranslational modification. The expression patterns of two distinct sea cucumber C3 genes, AjC3-2 and AjC3, were similar. During the different development stages from unfertilized egg to juvenile of the sea cucumber, the highest expression levels of AjC3-2 and AjC3 genes were both found in late auricularia. In the adult, the highest expression of these two genes was observed in the coelomocytes and followed by the body wall. AjC3-2 and AjC3 genes expression increased significantly at 6?h after the LPS challenge. These results indicated that these two C3 genes play a pivotal role in immune responses to the bacterial infection in sea cucumber.     

Observations on the division characterization of diploid nuclear in <Emphasis Type="Italic">Porphyra</Emphasis> (Bangiales,Rhodophyta)

Nuclear divisions of carpospores, conchocelis and conchospores of Porphyra yezoensis, P. haitanensis, P. katadai var. hemiphylla and P. oligospermatangia from China were investigated. The observations showed diploid chromosome numbers of 2n = 6 for P. yezoensis and P. oligospermatangia, and 2n = 10 for P. haitanensis and P. katadai var. hemiphylla. For all four species, somatic pairing of chromosome sets was observed in late prophase. Sister chromosomes separated at anaphase as mitosis took place in carpospores, conchocelis filamentous cells, conchosporangial branch cells and sporangial cells (conchospore formation). Chromosome configurations of tetrad and ring-shaped in conchospore germination were observed, demonstrating the occurrence of meiosis. The characteristics of diploid nuclear division in 2n = 6 species are the same as those of 2n = 10 species. The influence of somatic pairing on nuclear division of diploid cells in Porphyra was discussed.     

Polarization and Filter Properties Investigation of Metal Gratings and Rings

We demonstrated the near-field optical transmission properties of nanogratings with spoke and rings structures through a near-field scanning optical microscope, and the far-field optical transmission properties with different polarization angles are investigated with an optical microscope. Our experimental results verified the polarization properties of the nanograting structures and further demonstrated the experimental results are supported by the finite difference time domain theoretical simulation. The optical microscope imaging of the spoke and ring structures also show that the grating structures can disperse visible light of different wavelengths.     

Biobased poly(propylene sebacate) as shape memory polymer with tunable switching temperature for potential biomedical applications

From the point of better biocompatibility and sustainability, biobased shape memory polymers (SMPs) are highly desired. We used 1,3-propanediol, sebacic acid, and itaconic acid, which have been industrially produced via fermentation or extraction with large quantities as the main raw materials for the synthesis of biobased poly(propylene sebacate). Diethylene glycol was used to tailor the flexibility of the polyester. The resulted polyesters were found to be promising SMPs with excellent shape recovery and fixity (near 100% and independent of thermomechanical cycles). The switching temperature and recovery speed of the SMPs are tunable by controlling the composition of the polyesters and their curing extent. The continuously changed switching temperature ranging from 12 to 54 °C was realized. Such temperature range is typical for biomedical applications in the human body. The molecular and crystalline structures were explored to correlate to the shape memory behavior. The combination of potential biocompatibility and biodegradability of the biobased SMPs makes them suitable for fabricating biomedical devices.     

Phylogeny of Prokaryotes and Chloroplasts Revealed by a Simple Composition Approach on All Protein Sequences from Complete Genomes Without Sequence Alignment

The complete genomes of living organisms have provided much information on their phylogenetic relationships. Similarly, the complete genomes of chloroplasts have helped to resolve the evolution of this organelle in photosynthetic eukaryotes. In this paper we propose an alternative method of phylogenetic analysis using compositional statistics for all protein sequences from complete genomes. This new method is conceptually simpler than and computationally as fast as the one proposed by Qi et al. (2004b) and Chu et al. (2004). The same data sets used in Qi et al. (2004b) and Chu et al. (2004) are analyzed using the new method. Our distance-based phylogenic tree of the 109 prokaryotes and eukaryotes agrees with the biologists tree of life based on 16S rRNA comparison in a predominant majority of basic branching and most lower taxa. Our phylogenetic analysis also shows that the chloroplast genomes are separated to two major clades corresponding to chlorophytes s.l. and rhodophytes s.l. The interrelationships among the chloroplasts are largely in agreement with the current understanding on chloroplast evolution.Reviewing Editor: Dr. John Oakeshott     

Inhibition of fatty acid synthase suppresses U-2 OS cell invasion and migration via downregulating the activity of HER2/PI3K/AKT signaling pathway in vitro

FASN plays an important role in the malignant phenotype of various tumors. Our previous studies show that inhibition FASN could induce apoptosis and inhibit proliferation in human osteosarcoma (OS) cell in vivo and vitro. The aim in this study was to investigate the effect of inhibition FASN on the activity of HER2/PI3K/AKT axis and invasion and migration of OS cell. The expression of FASN, HER2 and p-HER2(Y1248) proteins was detected by immunohistochemistry in OS tissues from 24 patients with pulmonary metastatic disease, and the relationship between FASN and p-HER2 as well as HER2 was investigated. The results showed that there was a positive correlation between FASN and HER2 as well as p-HER2 protein expression. The U-2 OS cells were transfected with either the FASN specific RNAi plasmid or the negative control RNAi plasmid. FASN mRNA was measured by RT-PCR. Western blot assays was performed to examine the protein expression of FASN, HER2, p-HER2(Y1248), PI3K, Akt and p-Akt (Ser473). Migration and invasion of cells were investigated by wound healing and transwell invasion assays. The results showed that the activity of HER2/PI3K/AKT signaling pathway was suppressed by inhibiting FASN. Meanwhile, the U-2OS cells migration and invasion were also impaired by inhibiting the activity of FASN/HER2/PI3K/AKT. Our results indicated that inhibition of FASN suppresses OS cell invasion and migration via down-regulation of the “HER2/PI3K/AKT” axis in vitro. FASN blocker may be a new therapeutic strategy in OS management.