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Background B7-homologue 3 (B7-H3), a recently identified immunoregulatory protein, has been shown to be overexpressed in human hepatocellular carcinoma (HCC). However, whether the dynamic expression pattern of B7-H3 contributes to early invasion of HCC is largely unknown. In addition, the biological roles of B7-H3 in HCC are still unclear. Herein, we are going to examine B7-H3 expression profile and its clinicopathological significance in primary and metastatic HCC, and further determine whether B7-H3 knockdown simulates different pathological states of HCC progression and metastasis. Methods Using immunohistochemistry, B7-H3 expression was studied on 116 HCC containing primary and metastatic HCCs. Survival curves and log-rank tests were used to test the association of B7-H3 expression with survival. HCC cells with B7-H3 depletion were established by RNA interference to investigate the effect of B7-H3 on cell proliferation, apoptosis, migration and invasion in vitro. Results Statistical analysis of clinical cases revealed that B7-H3 high expression group had inclinations towards late TNM stage, the presence of vascular invasion, lymph metastasis, and the formation of microsatellite tumors. Increased intensity of tumor B7-H3 staining was detected more significantly in metastatic HCC tumors. Consistently in experiments performed in vitro, B7-H3 was able to stimulate the wound healing, metastasis and invasion of hepatoma cells by targeting epithelial-to-mesenchymal transition (EMT) via JAK2/Stat3/Slug signaling pathway, while no obvious influence on cell growth and apoptosis. Conclusion B7-H3 in the regulation of the metastatic capacity of HCC cells makes itself a promising therapeutic target for anti-metastasis therapy.

B7 family members are aberrantly expressed on the human hepatocellular carcinoma (HCC) cell surface, and induce local and systemic immunosuppression. Tumor-associated macrophages (TAMs) are a significant immune cell subpopulation in HCC and may be induced to express co-inhibitory molecules including B7 homologue 3 (B7-H3). In the present study, 79.3% of the HCC tissue samples showed high expression of B7-H3 which was positively correlated with the number of TAMs in the evaluated cancer tissues. Furthermore, high levels of TAMs or B7-H3 were associated with a shorter survival time of the HCC patients. In vitro, B7-H3 expression was upregulated at both the mRNA and protein levels in phorbol 12-myristate 13-acetate (PMA)-induced THP-1 cells cocultured with HepG2 cells in a Transwell system. In addition, B7-H3 promoted PMA-induced THP-1 cells to differentiate into the M2 phenotype, with evidence of increases in arginase 1 (Arg1), vascular endothelial cell growth factor (VEGF) and macrophage-derived chemokine (CCL22) mRNA following coculture with HepG2 cells. However, this phenomenon was abrogated through knockdown of B7-H3 by RNA interference or by blocking the signal transducer and activator of transcription 3 (STAT3) signaling pathway. Overall, these results suggest that the B7-H3-mediated STAT3 signaling pathway is an important mechanism for inducing M2-type polarization of TAMs, which accelerates HCC development. Our findings may support the development of novel therapeutic strategies for HCC patients through the skewing of the TAM phenotype by targeting the B7-H3 signaling pathway.

A method was developed for analyzing broad spectrum small molecule metabolites in the serum of hepatocellular carcinoma (HCC) patients based on ultrafast liquid chromatography–ion trap–time of flight tandem mass spectrometry (UFLC-IT-TOF MS). Serum samples were collected from 80 HCC patients and healthy persons. After pretreatment process for protein precipitation, the supernatant was analyzed with the UFLC-IT-TOF MS to obtain information on the metabonomics of small molecules. The eight compounds of glycocholic acid, choline glycerophosphate, acetyl-L-phenylalanine, oleamide, tetradecanamide, acetylcarnitine, lysolecithin and glycochenodeoxycholic acid in the HCC group were identified with significant differences from those in the health group (P <0.01). By using multidimensional analysis of variation coefficient and principal component analysis for the repeatability and 48 h stability, the method was demonstrated to have good repeatability, excellent precision, and high stability, which can satisfy the metabonomics research requirement. The high throughput and practical usability of the method further shows perspective for metabonomic analysis of large-batch serum samples.

The cellular immunity has a profound impact on the status of hepatitis C virus (HCV) infection. However, the response of cellular immunity on the virological response in patients with antiviral treatment remains largely unclear. We aimed to clarify the response of peripheral T cells and monocytes in chronic hepatitis C patients with antiviral treatment. Patients with chronic hepatitis C were treated either with interferon alpha-2b plus ribavirin (n = 37) or with pegylated interferon alpha-2a plus ribavirin (n = 33) for up to 24 weeks. Frequencies of peripheral regulatory T-cells (Tregs), programmed death-1 (PD-1) expressing CD4+ T-cells or CD8+ T-cells and toll-like receptor (TLR) 3 expressing CD14+ monocytes were evaluated by flow cytometry in patients at baseline, 12 and 24 weeks following treatment and in 20 healthy controls. Frequencies of Tregs, PD-1 and TLR3 expressing cells were higher in patients than those in control subjects (P<0.05). Patients with complete early virological response (cEVR) showed lower Tregs, PD-1 expressing CD4+ or CD8+ T-cells than those without cEVR at 12 weeks (P<0.05). Patients with low TLR3 expressing CD14+ monocytes at baseline had a high rate of cEVR (P<0.05). Low peripheral TLR3 expressing CD14+ monocytes at baseline could serve as a predictor for cEVR of antiviral therapy in chronic HCV-infected patients. The cEVR rates were significantly increased in the patients with reduced circulating Tregs, PD-1 expressing CD4+ or CD8+ T-cells. Chinese Clinical Trial Registry ChiCTR10001090.

Primary sclerosing cholangitis (PSC) is a chronic autoimmune cholestatic liver disease, with intrahepatic and/or extrahepatic bile duct diffuse inflammation, fibrosis, focal or segmental stenosis as the main features. Eventually this disease leads to bile duct obstruction, biliary cirrhosis and liver failure. The detection and diagnosis rate of PSC are increasing year by year, thus PSC becomes the hot spot for the study of hepatic inflammatory diseases. In this paper, we especially put our focus on the recent progress about diagnosis and treatment of PSC, and some special cases, including primary sclerosing cholangitis-autoimmune hepatitis (PSCAIH), autoimmune pancreatitis (AIP), ductile of PCS. These should help clinicians make a appropriate diagnosis and give correct treatment for these diseases.

Background & Aims The cellular immunity has a profound impact on the status of hepatitis C virus (HCV) infection. However, the response of cellular immunity on the virological response in patients with antiviral treatment remains largely unclear. We aimed to clarify the response of peripheral T cells and monocytes in chronic hepatitis C patients with antiviral treatment. Methods Patients with chronic hepatitis C were treated either with interferon alpha-2b plus ribavirin (n = 37) or with pegylated interferon alpha-2a plus ribavirin (n = 33) for up to 24 weeks. Frequencies of peripheral regulatory T-cells (Tregs), programmed death-1 (PD-1) expressing CD4+ T-cells or CD8+ T-cells and toll-like receptor (TLR) 3 expressing CD14+ monocytes were evaluated by flow cytometry in patients at baseline, 12 and 24 weeks following treatment and in 20 healthy controls. Results Frequencies of Tregs, PD-1 and TLR3 expressing cells were higher in patients than those in control subjects (P<0.05). Patients with complete early virological response (cEVR) showed lower Tregs, PD-1 expressing CD4+ or CD8+ T-cells than those without cEVR at 12 weeks (P<0.05). Patients with low TLR3 expressing CD14+ monocytes at baseline had a high rate of cEVR (P<0.05). Conclusions Low peripheral TLR3 expressing CD14+ monocytes at baseline could serve as a predictor for cEVR of antiviral therapy in chronic HCV-infected patients. The cEVR rates were significantly increased in the patients with reduced circulating Tregs, PD-1 expressing CD4+ or CD8+ T-cells. Trial Registration Chinese Clinical Trial Registry ChiCTR10001090.

Dohrniphora cornuta (Bigot) is a forensically important phorid fly indoors and in burial environments. The determination of a minimum postmortem interval (PMImin) often relies on the determination of the age of the immatures. Although the larval development data of D. cornuta under different temperatures has been established, the intrapuparial stage which lasts for about half of the total immature development is scarce. In this study, we investigated the key morphological changes during intrapuparial development at constant temperatures (15, 18, 21, 24, 27, 30, 33, and 36°C), with an aim to estimate the intrapuparial age of D. cornuta. Puparia were sampled at 12-h (24, 27, 30, and 33°C), 24-h (18 and 21°C), and 48-h (15°C) intervals. The morphological developments within the puparium were analyzed using a stereomicroscope after the puparium was removed. The average minimum duration of intrapuparial stage was inversely related to temperature, ranging from 184.79 ± 3.00 h at 30°C to 1102.86 ± 25.55 h at 15°C for female, and 197.40 ± 4.12 h at 30°C to 1175.33 ± 18.55 h at 15°C for male. It did not develop at 36°C. Some morphological traits that changed during development within the puparium could be used as age markers. According to these changes, the intrapuparial stage of D. cornuta was divided into nine stages which could be used for both sexes. This study provides relatively systematic development data of D. cornuta intrapuparial for the estimation of PMImin in forensic entomology.

The mitochondrial genome is frequently used for species identification and phylogenetic studies. In this study, we first sequenced and annotated the complete mitochondrial genomes of two phorid species that are forensically important in buried or enclosed environments: Metopina sagittata (Liu) and Puliciphora borinquenensis (Wheeler). The complete mitochondrial genome sequences of M. sagittata and P. borinquenensis were 15,640 bp with an A+T content of 75.97% and 15,429 bp with an A+T content of 75.38%, respectively. Their circular genomes both contained 13 protein-coding genes (PCGs), 22 transfer RNA genes, 2 ribosomal RNA genes, and 1 control region located between rrnS and trnI which was 808 bp for M. sagittata and 746 bp for P. borinquenensis. All the PCGs of both species started with ATN codons except for cox1 which usedTTG codon. In addition to the common stop codonTAA andTAG, the incomplete stop codonT was used in two PCGs (cox1 and nad4) of M. sagittata and five PCGs (cox1, cox2, cox3, nad5, and nad4) of P. borinquenensis.There were 3 and 10 mismatched base pairs in the tRNA secondary structures from M. sagittata and P. borinquenensis, respectively. Both maximum likelihood and Bayesian inference analyses indicated that Platypezidae and Phoridae are sister taxa. M. sagittata is closely related to P. borinquenensis within the subfamily Metopininae. This work enhances the databases of Phoridae genomes and contributes to the further study of species identification and phylogenetics of this family.