Differences of the immune cell landscape between normal and tumor tissue in human prostate.

BACKGROUND: Over the past few decades, immunological checkpoint therapy has been an increasingly prominent strategy in the treatment of tumors, including prostate cancer (PC). There are few systematic studies of the phenotypic of tumor-infiltrating immune cells in PC tissues. METHODS: CIBERSORT is an analytical tool for estimating the abundance of member cell types in mixed cell population by gene expression data. Herein, we analyzed different levels of tumor-infiltrating immunity cells in normal tissue compared with PC using CIBERSORT. RESULTS: The results showed that proportion of M1 macrophages and resting mast cells presented significant differences in prostate tumor than these normal tissues. A higher proportion of resting mast cells was associated with a worse outcome and M1 macrophages was associated with a favorable outcome. Moreover, the radiotherapy and targeted molecular therapy can affect the immune infiltration of M1 macrophages and resting mast cells. CONCLUSIONS: Resting mast cells and M1 macrophages has an important role in the prognosis of prostate cancer. Our data provides valuable information about the future treatment of PC.

Phylogenetic analysis of the Mongolian gerbil (Meriones unguiculatus) from China based on mitochondrial genome.

Meriones unguiculatus (Gerbillinae, Rodentia) is widely used as an animal model of human disease. Here, we provide the first report of the complete mitochondrial genome sequence of M. unguiculatus (GenBank accession Nos. KF425526 and NC_023263). The sequence contained the conserved vertebrate pattern of 13 protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs, and 1 major noncoding region. We identified one extended termination-associated sequence and one conserved sequence block in the non-coding region. The putative origin of replication for the light strand (OL) was 35 bp long. The OL stem and adjacent sequences were highly conserved, but the loop region differed from those of other rodent species. Base composition and codon usage of the 13 protein-coding genes in M. unguiculatus were compared with those of 23 rodent species with previously sequenced mitochondrial genomes. An A+T content of 63.0% was present in M. unguiculatus; this is similar to the Murinae average (62.4 ± 0.8%) and falls between the average for Mus musculus (63.1 ± 0.1%) and Rattus sp (61.7 ± 0.4%). The AT and GC skew values of M. unguiculatus were 0.035 and -0.28, respectively, similar to those of Cricetinae species (0.057 ± 0.05 and -0.31 ± 0.05). The codon families exhibited similar abundance in all 24 species. Analysis of phylogenetic relationships with 23 other rodent species using neighbor-joining and maximum likelihood protocols and the 12 protein-coding regions on the H strand showed that M. unguiculatus should be classified as genus Meriones, sub-family Gerbillinae, family Muridae.

Cyclic adenosine monophosphate-protein kinase A signal pathway may be involved in pulmonary aquaporin-5 expression in ischemia/reperfusion rats following deep hypothermia cardiac arrest.

We investigated the effects of cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) on the expression of aquaporin 5 (AQP5) in ischemia/reperfusion (I/R) rats following deep hypothermia cardiac arrest. Wistar rats were randomly divided into: a sham control group (subjected to a sham operation); an I/R group (subjected to occlusion of the bronchial arteries and the left inferior pulmonary artery); an H89 group (subjected to occlusion of the bronchial arteries and the left inferior pulmonary vein and artery, and treated with 5 mg/kg H89 for 2 days before the study); and a forskolin group (subjected to occlusion of the bronchial arteries and the left inferior pulmonary vein and artery, and treated with 5 mg/kg forskolin for 2 days before the study). Expression levels of AQP5 mRNA and protein were determined using reverse transcription-polymerase chain reaction and western blotting. Decreased expression of AQP5 was noted in the pulmonary tissues of the I/R group compared with the sham controls. Compared to that in the control group, there was a notable decrease in AQP5 expression in the I/R group. After treating with forskolin, AQP5 expression increased in the forskolin group compared with the I/R group. In the H89 group, AQP5 expression decreased compared with the I/R group. The decreased expression of AQP5 was possibly associated with acute pulmonary injury induced by I/R. The cAMP-PKA signal pathway may be involved in the expression of AQP5 in I/R rats after deep hypothermia cardiac arrest.

Expression of macrophage migration-inhibitory factor in duodenal ulcer and its relation to Helicobacter pylori infection.

The aim of this study was to examine the expression of macrophage migration-inhibitory factor (MIF) in duodenal ulcer epithelial cells and its relation to Helicobacter pylori (Hp) infection, and to discuss the pathogenic roles of MIF expression and Hp infection in duodenal ulcer. MIF protein and mRNA expression was examined in samples from patients with duodenal ulcer with and without Hp infection (N = 40 each, experimental group), and in normal duodenal bulb mucosal tissue (N = 40, control group) using immunohistochemistry and in situ hybridization. Patients without Hp infection received routine treatment, and treatment was provided to the patients positive for Hp to eradicate Hp infection. Hp and MIF expression levels before treatment and after the ulcer had been cured were compared. The positive rates of MIF protein and mRNA in patients with Hp infection before treatment were 67.5 and 65%, respectively, and were 18.9 and 21.6% in the 37 patients from whom Hp was eliminated. These were statistically different both before and after treatment compared with controls (P < 0.05). In the patients without Hp infection, the positive rates of MIF protein and mRNA expression before (45 and 47.5%, respectively) and after (32.5 and 30%) treatment were not significantly different (P > 0.05). The results of this study suggested that MIF is related to the development of duodenal ulcer, and that the presence of Hp is closely related with the expression of MIF in the duodenal mucosa and the development of duodenal ulcer.

Marker-assisted selection in breeding silkworm strains with high tolerance to fluoride, scaleless wings, and high silk production.

In the silkworm (Bombyx mori), tolerance to fluoride and scaleless wings are controlled by the dominant gene Dtf (dominant tolerance to fluoride) and recessive gene nlw (no Lepidoptera wings), respectively, and these genes have been mapped by using simple sequence repeat and sequence tag site markers. Marker-assisted evaluation and selection of silkworms with fluoride tolerance and scaleless wings were used for predicting fluoride resistance and scaleless wings in backcrossed animals. A silkworm strain was bred using this method, and its economic characteristics were found to be similar to those of commercial silkworms. These methods will therefore be useful for silkworm breeding programs and in screening for two or more characteristics of interest for segregating populations.

CTLA4 enhances the osteogenic differentiation of allogeneic human mesenchymal stem cells in a model of immune activation

Allogeneic mesenchymal stem cells (allo-MSCs) have recently garnered increasing interest for their broad clinical therapy applications. Despite this, many studies have shown that allo-MSCs are associated with a high rate of graft rejection unless immunosuppressive therapy is administered to control allo-immune responses. Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is a co-inhibitory molecule expressed on T cells that mediates the inhibition of T-cell function. Here, we investigated the osteogenic differentiation potency of allo-MSCs in an activated immune system that mimics the in vivo allo-MSC grafting microenvironment and explored the immunomodulatory role of the helper T cell receptor CTLA4 in this process. We found that MSC osteogenic differentiation was inhibited in the presence of the activated immune response and that overexpression of CTLA4 in allo-MSCs suppressed the immune response and promoted osteogenic differentiation. Our results support the application of CTLA4-overexpressing allo-MSCs in bone tissue engineering.

CTLA4 enhances the osteogenic differentiation of allogeneic human mesenchymal stem cells in a model of immune activation.

Allogeneic mesenchymal stem cells (allo-MSCs) have recently garnered increasing interest for their broad clinical therapy applications. Despite this, many studies have shown that allo-MSCs are associated with a high rate of graft rejection unless immunosuppressive therapy is administered to control allo-immune responses. Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is a co-inhibitory molecule expressed on T cells that mediates the inhibition of T-cell function. Here, we investigated the osteogenic differentiation potency of allo-MSCs in an activated immune system that mimics the in vivo allo-MSC grafting microenvironment and explored the immunomodulatory role of the helper T cell receptor CTLA4 in this process. We found that MSC osteogenic differentiation was inhibited in the presence of the activated immune response and that overexpression of CTLA4 in allo-MSCs suppressed the immune response and promoted osteogenic differentiation. Our results support the application of CTLA4-overexpressing allo-MSCs in bone tissue engineering.

Effects of rifampicin on osteogenic differentiation and proliferation of human mesenchymal stem cells in the bone marrow.

This study was designed to investigate the effect of different concentrations of rifampicin on osteogenic differentiation and proliferation of mesenchymal stem cells (MSCs) in human bone marrow. Rifampicin treatment at 0, 4, 8, 16, 32, 64, and 128 mg/mL was applied throughout the whole process, from stromal cells purified from human bone marrow to differentiated bone cells. The effect of rifampicin on MSC proliferation was determined using the MTT assay. The effect of rifampicin on the expressions of type I collagen (COL1A1), osteopontin/bone Gla protein (OPN/BGP), and alkaline phosphatase (ALP) in human osteoblast cells were determined by real-time polymerase chain reaction, and the expressions of COL1A1, OPN/BGP, and the runt-related transcription factor (RUNX2) were determined by Western blot. Results showed that the proliferation of MSCs was significantly inhibited when the rifampicin concentration exceeded 32 mg/mL. In addition, increased rifampicin concentrations inhibited the formation of calcium nodules, OPN/BGP, and COL1A1 in osteoblasts after 28 days of induction. The RNA expressions of OPN/BGP, COL1A1, and ALP were significantly downregulated compared to those of the control group in osteoblasts after induction. The protein expressions of RUNX2, COL1A1, and OPN/BGP were also significantly downregulated compared to those of the control group after induction. In conclusion, rifampicin at exorbitant concentration exerts adverse effects on the proliferation of MSCs in human bone marrow and the differentiation of osteoblasts.

Seventeen polymorphic microsatellite markers developed for the Javelin goby, Synechogobius hasta (Gobiidae).

Synechogobius hasta is an important commercial marine fish with distinctive features of rapid growth and short lifespan. We isolated and characterized 17 microsatellite markers for S. hasta using a (GT)(13)-enriched genomic library. Polymorphism was assessed in 48 individuals from a single population collected from the northern coastal waters of the Yellow Sea. The number of alleles per locus ranged from 2 to 23, with a mean of 11.3. The observed and expected heterozygosities ranged from 0.130 to 1.000 and from 0.123 to 0.939, with means of 0.758 and 0.774, respectively. Fourteen of 17 loci conformed to Hardy-Weinberg equilibrium and no significant linkage disequilibrium between locus pairs was detected. These microsatellite markers will be useful for population genetic structure analyses.