Expression of 10 circulating cytokines/chemokines in HBV-related liver disease.

BACKGROUND: Cytokines/chemokines play essential roles in the occurrence and progression of hepatitis B virus (HBV) infection. This study aimed to observe the expression patterns of 10 related cytokines/chemokines in the serum of healthy individuals, self-limited patients and HBV-infected patients at different stages of disease (chronic hepatitis B (CHB), liver cirrhosis (LC), hepatocellular dysplastic nodules (DNs) and hepatocellular carcinoma (HCC)) and to analyze the relationships of these cytokines/chemokines with disease progression. METHODS: The levels of six cytokines (FGF-2, IFN-α2, IL-4, IL-6, IL-10 and VEGF-A) and four chemokines (GRO-α, IL-8, IP-10 and MCP-1) were quantified using Luminex multiplex technology. RESULTS: There were no significant differences in the expression of the 10 cytokines/chemokines between healthy individuals and self-limited patients. The levels of IL-4, IL-6, and IL-8 increased significantly in the CHB and LC groups. IL-10 was highly expressed in the HCC group. The level of IP-10 was significantly greater in all liver disease groups (CHB, LC, DN and HCC) than in the HI and SL-HBV groups, while the level of GRO was significantly lower in all liver disease groups than in the HI and SL-HBV groups. The levels of the 10 cytokines/chemokines were not significantly different between the preoperative group and the two-day postoperative group. Significant increases in the levels of IL-4, VEGF-A and IL-8 and significant decreases in those of IL-10 and GRO-α were observed 3 months after surgery. Correlation analysis revealed that most of the cytokines/chemokines with significant correlation differences were positively correlated before and after HCC surgery. CONCLUSION: Our results highlight the fluctuating status of specific cytokines in HBV infection-related disease progression. It is speculated that these cytokines may be used as serum markers to monitor dynamic changes during the progression of HBV-related liver disease and to predict patient prognosis.

Skeletal Editing of Benzene Motif: Photopromoted Transannulation for Synthesis of DNA-Encoded Seven-Membered Rings.

In this report, we present a photopromoted, metal-free transannulation of phenyl azides for the synthesis of DNA-encoded seven-membered rings. The transformation is efficiently achieved through a skeletal editing strategy targeting the benzene motif coupled with a Reversible Adsorption to Solid Support (RASS) strategy. A variety of valuable DNA-encoded seven-membered ring compounds, including DNA-encoded 3H-azepines, azepinones, and unnatural amino acids, are now accessible. Crucially, this DNA-compatible protocol can also be applied for the introduction of complex molecules, as exemplified by Lorcaserin and Betahistine. The selective conversion of readily available phenyl rings into high-value seven-membered rings offers a promising avenue for the construction of diversified and drug-like DNA-encoded library.

Radical C-H Sulfonation of Arenes: Its Applications on Bioactive and DNA-Encoded Molecules.

The photocatalyst-free electron donor-acceptor (EDA) complex photochemistry was deemed to expand the potential of photodriven radical chemistry. Here, we report a cross-coupling reaction of thianthrenium salt functionalized arenes and sodium sulfinates via a photopromoted single electron transfer (SET) process of an EDA complex. A series of biarylsulfones were obtained with high site-selectivity and reactivity. This mild and practical radical reaction could be applied on the bioactive and DNA-encoded molecules.

Acute effect of high-intensity interval exercise on vascular endothelial function and possible mechanisms of wall shear stress in young obese males.

Objective: To investigate the mechanisms of wall shear stress (WSS) responsible for the effects of high-intensity interval exercise (HIIE) on vascular endothelial function in young obese males. Methods: A within-subject study design was used. We examined the response of the reactive hyperemia index (RHI) to acute HIIE in young obese males (n = 20, age = 20.38 ± 1.40 years, body mass index [BMI] = 31.22 ± 3.57, body fat percentage [BF (%)] = 31.76 ± 3.57). WSS was manipulated using 100, 80, or 60 mmHg cuff inflation during the HIIE to determine the proper inflation capable of maintaining WSS near baseline levels. One-way repeated measures analysis of variance and LSD post hoc tests were performed to compare changes in WSS and vascular endothelial function at baseline HIIE and following HIIE using different cuff inflations. Results: There were no significant differences in RHI and WSS between the three cuff inflation values (p > 0.05). WSS was significantly higher in obese male individuals after HIIE and HIIE with 100 mmHg cuff inflation (p = 0.018, p = 0.005) than that at baseline, with no significant differences observed comparing HIIE and HIIE with 100 mmHg inflation (p = 0.23). The RHI after HIIE was significantly higher (p = 0.012) than that at baseline, while no significant differences were detected after HIIE at 100 mmHg (p = 0.91). The RHI was significantly lower after HIIE with 100 mmHg than that after HIIE (p = 0.007). WSS (p = 0.004) and RHI (p = 0.017) were significantly higher after HIIE than that at baseline, while no significant differences were observed after HIIE with either 80 or 60 mmHg cuff inflation (baseline vs. HIIE + 80 mmHg: WSS: p = 0.33, RHI: p = 0.38; baseline vs. HIIE + 60 mmHg: WSS: p = 0.58, RHI: p = 0.45). WSS was similar to HIIE, after HIIE with either 80 or 60 mmHg inflation (p = 0.36, p = 0.40). However, RHI was significantly higher for HIIE than for HIIE with both 80 and 60 mmHg inflation (p = 0.011, p = 0.006). Conclusion: HIIE could significantly improve WSS and vascular endothelial function. HIIE intervention with 60 or 80 mmHg inflation might enhance WSS near the baseline level. HIIE-induced acute changes in WSS may provide the primary physiological stimulus for vascular endothelial adaptation to HIIE in young obese males.

The effects of high-intensity interval training and moderate-intensity continuous training on visceral fat and carotid hemodynamics parameters in obese adults.

Objectives: The present study aimed to examine the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on visceral fat and hemodynamic parameters in obese adults. Methods: Fifty-two males were included in this study and divided into three groups: HIIT group (n = 21, age = 20.86 ± 1.62 years, BF (%) = 30.10 ± 5.02), MICT group (n = 22, age = 20.76 ± 1.14 years, BF (%) = 30.19 ± 5.76), and control group (CON) (n = 9, age = 21.38 ± 1.77 years, BF (%) = 30.40 ± 5.10). The HIIT and MICT groups received the exercise intervention three to four times per week for eight weeks (HIIT: exercise intensity 80-95% HRmax, circuit; MICT: exercise intensity 60-70% HRmax, running), and the control (CON) group received health education and guidance without exercise intervention. The body compositions and serum lipid indexes were tested to calculated LAP and VAI. The color doppler ultrasound diagnostic technology was used to test the artery diameter and blood velocity before and after the intervention. Based on the test data, MATLAB software and Womersley theory were used to calculate the hemodynamic parameters of the common carotid artery, including wall shear stress, flow rate, blood pressure, oscillatory shear index, elasticity modulus, dynamic resistance, artery diameter, arterial stiffness, circumferential strain and pulsatility index. Results: We found that lipid accumulation product (LAP) was significantly decreased in both the HIIT group (p < 0.01) and MICT (p < 0.05) group but not in the CON group (p > 0.05). In contrast, visceral adiposity index (VAI) decreased in both the HIIT and MICT groups and increased in the CON group, although the difference among groups was not significant (p > 0.05). After 8 weeks of intervention, the blood velocity and wall shear stress were greater after HIIT and MICT intervention (p < 0.01). Artery diameter, oscillatory shear index, arterial stiffness, and pulsatility index decreased significantly, and circumferential strain increased significantly in the HIIT group (all, p < 0.01, p < 0.05) but not in the MICT group (p > 0.05). Dynamic resistance was significantly decreased in the MICT group. There was no difference in the CON group after the period of intervention (all, p > 0.05). LAP was positively related to artery diameter (r = 0.48, p = 0.011), blood pressure (r = 0.46, p = 0.002), flow rate (r = 0.31, p = 0.04), oscillatory shear index (r = 0.44, p = 0.03), and elasticity modulus (r = 0.33, p = 0.029) but inversely related to circumferential strain (r = -0.36, p = 0.028). The VAI was also positively associated with artery diameter (r = 0.33, p = 0.03), elasticity modulus (r = 0.38, p = 0.009), and arterial stiffness (r = 0.39, p = 0.012). In addition, the VAI was negatively correlated with the circumferential strain (r = -0.33, p = 0.04). Conclusion: The present study demonstrated that both HIIT and MICT exercises for 8 weeks could effectively enhance visceral fat indices and partial hemodynamic parameters. Therefore, HIIT and MICT exert important effects on reducing fat content and improving hemodynamic environment. But HIIT on oscillatory shear index, arterial stiffness, circumferential strain, and pulsatility index was superior to MICT. In addition, there are close correlations between visceral fat and partial hemodynamic parameters of the common carotid artery.

Mechanism and Protection of Radiotherapy Induced Sensorineural Hearing Loss for Head and Neck Cancer.

PURPOSE: Radiotherapy-induced sensorineural hearing loss (RISNHL) is a common adverse effect in patients with head and neck cancer. Given that there are few studies on the pathogenesis of RISNHL at present, we summarized the possible pathogenesis of RISNHL and possible protective measures found at present by referring to relevant literatures. METHODS: We performed a comprehensive literature search in the PubMed database, using keywords "sensorineural hearing loss," "radiotherapy," and "cancer," among others. The literature was examined for the possible mechanism and preventive measures of sensorineural hearing loss induced by radiotherapy. RESULTS: We found that the incidence of RISNHL was closely related to the damage directly caused by ionizing radiation and the radiation-induced bystander effect. It also depends on the dose of radiation and the timing of chemotherapy. Studies confirmed that RISNHL is mainly involved in post-RT inflammatory response and changes in reactive oxygen species, mitogen-activated protein kinase, and p53 signaling pathways, leading to specific manners of cell death. We expect to reduce the incidence of hearing loss through advanced radiotherapy techniques, dose limitation of organs at risk, application of cell signaling inhibitors, use of antioxidants, induction of cochlear hair cell regeneration, and cochlear implantation. CONCLUSION: RISNHL is associated with radiation damage to DNA, oxidative stress, and inflammation of cochlear cells, stria vascularis endothelial cells, vascular endothelial cells, spiral ganglion neurons, and other supporting cells. At present, the occurrence mechanism of RISNHL has not been clearly illustrated, and further studies are needed to better understand the underlying mechanism, which is crucial to promote the formulation of better strategies and prevent the occurrence of RISNHL.

The impact of acute exercise on implicit cognitive reappraisal in association with left dorsolateral prefronta activation: A fNIRS study.

Despite findings showing that acute exercise may help enhance emotion regulation, the neurophysiological mechanisms of these effects remain poorly understood. In this study, we examined whether acute exercise influences cognitive emotion regulation, and, in particular, an implicit cognitive reappraisal. Twenty sedentary young women were randomly assigned to either a control group (n = 10) or an exercise group (n = 10). Participants underwent an implicit cognitive reappraisal task twice, before and after the 30-min acute exercise or control, alongside functional near-infrared spectroscopy recordings (NIRS). The left dorsolateral prefrontal cortex (dlPFC) and left orbital frontal cortex (OFC) were activated during implicit cognitive reappraisal at baseline, but only the left dlPFC activation was linked with behavioral performance. Acute exercise enhanced the activation of these regions, reflective of the partial neural bases of implicit cognitive reappraisal, in the left dlPFC and left OFC, but did not alter the behavioral performance. Results also showed that acute exercise moderated the positive effect of left dlPFC activation on implicit cognitive reappraisal performance; specifically, this effect was stronger in the exercise group. In conclusion, the enhanced activation of the left dlPFC by acute exercise and the increased link between behavioral performance and its neural indices may point to acute exercise as a promoter of implicit cognitive reappraisal.

Three-dimensional hydrogel culture conditions promote the differentiation of human induced pluripotent stem cells into hepatocytes.

BACKGROUND AIMS: Human induced pluripotent stem cells (hiPSCs) are becoming increasingly popular in research endeavors due to their potential for clinical application; however, such application is challenging due to limitations such as inferior function and low induction efficiency. In this study, we aimed to establish a three-dimensional (3D) culture condition to mimic the environment in which hepatogenesis occurs in vivo to enhance the differentiation of hiPSCs for large-scale culture and high throughput BAL application. METHODS: We used hydrogel to create hepatocyte-like cell (HLC) spheroids in a 3D culture condition and analyzed the cell-behavior and differentiation properties of hiPSCs in a synthetic nanofiber scaffold. RESULTS: We found that treating cells with Y-27632 promoted the formation of spheroids, and the cells aggregated more rapidly in a 3D culture condition. The ALB secretion, urea production and glycogen synthesis by HLCs in 3D were significantly higher than those grown in a 2-dimensional culture condition. In addition, the metabolic activities of the CYP450 enzymes were also higher in cells differentiated in the 3D culture condition. CONCLUSIONS: 3D hydrogel culture condition can promote differentiation of hiPSCs into hepatocytes. The 3D culture approach could be applied to the differentiation of hiPSCs into hepatocytes for bioartificial liver.

Low density lipoprotein receptor class A domain containing 4 (LDLRAD4) promotes tumorigenesis of hepatic cancer cells.

LDLRAD4 was previously identified and shown to be connected with psychiatric disorders. The structure of LDLRAD4 protein is similar to that of TMEPAI protein, which is overexpressed in many tumors. However, it is still unknown whether LDLRAD4 is involved in tumorigenesis. In this study, the potential role of LDLRAD4 in tumorigenesis was investigated. LDLRAD4 is elevated in hepatic cancer cells and tumor tissues, and expression of LDLRAD4 promotes hepatic cancer cell HepG2 and SMMC-7721 proliferation and migration. LDLRAD4 interacts Nedd4 to promote cell proliferation and migration and negatively regulates the TGF-ß signaling. Furthermore, immunofluorescence microscopy analysis indicates that LDLRAD4 is localized to the lysosome and association with Nedd4 is necessary for its intracellular transport to the lysosome. In addition, depletion of LDLRAD4 in HepG2 liver cancer cells inhibited tumorigenesis in nude mice. These results reveal an oncogenic role of LDLRAD4 in tumorigenesis through its association with Nedd4.

Overexpression of microRNA let-7 correlates with disease progression and poor prognosis in hepatocellular carcinoma.

The aim of the study was to explore the clinical significance of let-7 expression in hepatocellular carcinoma (HCC).A PCR array was conducted to screen for let-7 expression in early-stage HCC. Next, the deregulation of let-7 was confirmed by quantitative real-time RT-PCR (qRT-PCR) in another set of liver tissues, including normal control (NC), chronic hepatitis (CH), liver cirrhosis (LC), HCC, and adjacent nontumor (NT) tissues. In addition, as the potential target mRNA of let-7, alpha 2(I) collagen (COL1A2) mRNA was also quantified in the above liver tissues. Finally, an association study comparing let-7 and COL1A2 and their clinical significance in HCC was conducted.PCR array analysis revealed that the expression levels of let-7a/7b/7c were significantly downregulated in early-stage HCC compared to those in NT tissues. As compared to NC samples, qRT-PCR further confirmed that let-7a/7b/7c/7e were significantly upregulated in CH, LC, and NT tissues, while there were no significant differences in expression between the HCC and NC groups. Although COL1A2 may be the target mRNA of let-7, only let-7c expression was inversely correlated with COL1A2 mRNA expression in CH tissues. In HCC tissues, levels of let-7a/7b/7c/7e were positively correlated with that of COL1A2 mRNA. The clinical significance study revealed that elevated let-7a expression was significantly correlated with serosal and vein invasion, while elevated let-7c expression was significantly correlated with vein invasion and advanced TNM stage. Elevated let-7e expression was significantly correlated with vein invasion in HCC. Significantly shorter postoperative overall survival was observed in HCC patients with high let-7c expression.The results suggest that aberrant expression of let-7a/7b/7c/7e occurs in benign liver diseases and HCC. The upregulation of let-7 expression is associated with the progression and poor prognosis of HCC, and further mechanistic studies are warranted.

Profiles of differential expression of circulating microRNAs in hepatitis B virus-positive small hepatocellular carcinoma.

BACKGROUND: Abnormally expressed circulating microRNA (miRNA) may serve as a potential biomarker for the diagnosis of cancer patients. OBJECTIVE: We sought to determine the differentially expressed circulating microRNAs in patients with hepatitis B virus (HBV)-positive small hepatocellular carcinoma (HCC) compared to other HBV-positive benign liver diseases. METHODS: The miScript miRNA PCR Array was used to detect the levels of 84 miRNAs in plasma or serum samples of patients with HBV-related small HCC (23 cases), liver cirrhosis (LC) (20 cases), chronic hepatitis B (CHB) (20 cases) and healthy controls (16 cases). MiRNAs with fold-change values ⩾ 2 or ⩽ 0.5 compared to healthy controls were considered to be deregulated miRNAs. RESULTS: The results of duplicate plasma experiments were not reliable. Comprehensive analysis of the two serum experiments showed that the quality controls all met the requirements. We found 18 differentially expressed miRNAs. Relative to healthy controls, nine, three, and 11 miRNAs were up-regulated in the CHB group, LC group and small HCC group, respectively. In contrast, one, three, and three miRNAs were down-regulated in the same patient groups, respectively. Interestingly, miR-195, miR-25 and miR-16 were up-regulated, and miR-205 was down-regulated, in all three experimental groups. Moreover, only in the HCC group, miR-18a, miR-100, miR-145 and miR-223 were up-regulated 3.48-, 2.95-, 2.12- and 3.91-fold, respectively, and miR-200a and miR-222 were down-regulated 2.56- and 2.00-fold, respectively. CONCLUSIONS: Our study demonstrated the presence of six differentially expressed serum microRNAs in HBV-positive small HCC compared to other benign liver diseases associated with HBV.

Constructing a dense genetic linkage map and mapping QTL for the traits of flower development in Brassica carinata.

KEY MESSAGE: An integrated dense genetic linkage map was constructed in a B. carinata population and used for comparative genome analysis and QTL identification for flowering time. An integrated dense linkage map of Brassica carinata (BBCC) was constructed in a doubled haploid population based on DArT-Seq(TM) markers. A total of 4,031 markers corresponding to 1,366 unique loci were mapped including 639 bins, covering a genetic distance of 2,048 cM. We identified 136 blocks and islands conserved in Brassicaceae, which showed a feature of hexaploidisation representing the suggested ancestral crucifer karyotype. The B and C genome of B. carinata shared 85 % of commonly conserved blocks with the B genome of B. nigra/B. juncea and 80 % of commonly conserved blocks with the C genome of B. napus, and shown frequent structural rearrangements such as insertions and inversions. Up to 24 quantitative trait loci (QTL) for flowering and budding time were identified in the DH population. Of these QTL, one consistent QTL (qFT.B4-2) for flowering time was identified in all of the environments in the J block of the B4 linkage group, where a group of genes for flowering time were aligned in A. thaliana. Another major QTL for flowering time under a winter-cropped environment was detected in the E block of C6, where the BnFT-C6 gene was previously localised in B. napus. This high-density map would be useful not only to reveal the genetic variation in the species with QTL analysis and genome sequencing, but also for other applications such as marker-assisted selection and genomic selection, for the African mustard improvement.

Analysis of microRNA expression profiles in human hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: Increasing evidence has shown that the deregulation of microRNAs (miRNAs) is closely related to the development and progression of hepatocellular carcinoma (HCC). To screen for HCC-specific miRNAs, this study investigated the differentially expressed miRNAs between HCC and matched non-tumorous tissue (NT). METHODS: This study analyzed the differential expression profiles of miRNAs in 11 pairs of HCC and matched NT from 11 hepatitis B virus (HBV) infection patients with the RT2 miRNA PCR array containing 88 human cancer-related miRNAs. The fold change value was more than two between the HCC and the matched NT, which indicated that there was deregulation of miRNAs. The down-regulated let-7a was validated in another sample set of 34 tissues with the TaqMan RT-qPCR method. RESULTS: Compared with the matched NT tissues, 9 miRNAs were up-regulated in the HCC tissues, and three were considered statistically significant (p < 0.05): miR-96, miR-183, and miR-196a, which were up-regulated 4.746-, 7.127-, and 3.498-fold, respectively. Simultaneously, 9 miRNAs were down-regulated in the HCC tissues, and two were considered statistically significant: let-7c and miR-138, which were down-regulated 3.945- and 4.790-fold, respectively. The expression levels of let-7a were 1.071 +/- 0.401, 0.926 +/- 0.477, 0.881 +/- 1.214, and 0.535 +/- 0.719 in the healthy group, chronic hepatitis B(CHB) group, NT group, and HCC group, respectively (p > 0.05). CONCLUSIONS: This study demonstrates that 18 miRNAs were deregulated in the HCC and matched NT tissues. The deregulated miRNAs suggest that further analyses with larger miRNA samples as a diagnostic marker are warranted.

Expression and significance of microRNA-183 in hepatocellular carcinoma.

OBJECTIVE: In our previous study, we found that some miRNAs were deregulated in hepatocellular carcinoma (HCC), including miR-183. However, the expression of miR-183 in the progression of benign liver diseases to HCC and its correlation with clinicopathologic factors remain undefined. METHODS: MiR-183 expression was measured in normal controls (NC) (n = 21), chronic viral hepatitis B or C (CH) tissues (n = 10), liver cirrhosis (LC) tissues (n = 18), HCC tissues (n = 92), and adjacent nontumor tissues (NT) (n = 92) by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR). RESULTS: The expression levels of miR-183 were significantly higher in HCC than in NT, LC, CH, and NL (P = 0.001, P < 0.001, P = 0.011, P < 0.001, resp.). The upregulated miR-183 in HCC was correlated with TNM stage (P = 0.042) and cirrhosis (P = 0.025). The Kaplan-Meier survival analysis showed that miR-183 expression was not associated with the survival of HCC patients. However, miR-183 yielded an area under the curve (AUC) of 0.808 with 59.8% sensitivity and 91.8% specificity in discriminating HCC from benign liver diseases (CH and LC) or NC. CONCLUSIONS: The upregulated miR-183 may associate with onset and progression of HCC, but not with the patient survival. A further research is needed to determine the potential of miR-183 as biomarker for HCC.

Expression and clinical significance of livin protein in hepatocellular carcinoma.

In this study, the two-step PV method of immunohistochemistry was used to determine livin protein expression in HCC tissues, pericarcinoma tissues, hepatitis/hepatic cirrhosis tissues, and normal hepatic tissues, and livin protein expression was detected in the blood plasma of patients with HCC before and after surgery, subjects with hepatic cirrhosis and hepatitis, and healthy blood donors using ELISA. Livin protein expression was significantly higher in HCC tissues than that in normal hepatic tissues and hepatitis/hepatic cirrhosis tissues, with no significant difference between HCC tissues and pericarcinoma tissues. The HCC patients with positive livin protein expression had a significantly higher survival rate than those with negative livin protein expression. Livin protein expression was significantly higher in the blood plasma of patients with HCC before and after surgery and in patients with hepatic cirrhosis and hepatitis than that in healthy blood donors, whereas livin protein expression in the blood plasma of patients with HCC was not significantly different from that of patients with hepatic cirrhosis and hepatitis. Livin protein expression in HCC tissues did not correlate with that in the blood plasma of the same HCC patients. Livin protein expression may be a potential, effective indicator for assessing prognosis in patients with HCC.

[Studies on the relationship between polymorphism of IL-28B rs8099917 and the outcome of HBV infection].

OBJECTIVE: To investigate the correlation between IL-28B rs8099917 polymorphism and the outcome of HBV infection. METHODS: Genotype of rs8099917 (T > G) in IL-28B locus was determined by TaqMan SNP genotyping from 486 individuals which including 199 chronic HBV carriers (including 100 HBV-induced liver cirrhosis and 99 HBV-related HCC). 143 people with self-limited infection and 144 healthy people served as controls. Multivariate analysis was used to assess the effect of IL-28B rs8099917 SNP among all the studied groups. RESULTS: Distribution of genotype and allele of the rs8099917 locus were in accordance with Hardy-Weinberg equilibrium in different groups or with the total population. The frequencies of the rs8099917 TT, GT, GG genotypes were 89.3%, 10.5% and 0.2%, and the frequency of allele T and G accounted for 94.5% and 5.5%, respectively. In respect of genotype or allele frequency, there was no significant differences found among the groups (P > 0.05). When comparing with the TT genotype, data from the multinomial logistic analysis showed that the ORs and (95%CI) of TG/GG genotypes were 1.589 (0.735 - 3.437), 1.351 (0.550 - 3.316) and 1.704 (0.717 - 4.052), respectively. The genotype frequencies in different groups with different clinical features showed that TG/GG genotypes significantly increased the risk of r-GTII(+) for individuals with HBV-related HCC (χ(2) = 17.534, P = 0.001), with OR as 14.821 (3.227 - 68.064). It was particularly so for males (χ(2) = 14.924, P = 0.014), with OR (95%CI) as 45.000 (2.772 - 730.571). CONCLUSION: IL-28B rs8099917 SNP had no correlation with the outcome of HBV infection.

Tissue factor-factor VIIa regulates interleukin-8, tissue factor and caspase-7 expression in SW620 cells through protease-activated receptor-2 activation.

The tissue factor-factor VIIa (TF/VIIa) complex is believed to activate protease-activated receptor-2 (PAR2) and to trigger the malignant behavior of various types of cancer cells. In our previous study, it was demonstrated that TF and PAR2 were overexpressed in high metastatic potential colon cancer cells (SW620). Both PAR2 agonist (SLIGKV-NH2, PAR2-AP) and factor VIIa facilitated SW620 cell proliferation and migration. In the present study, the molecular mechanisms of TF/VIIa-induced SW620 cell proliferation and migration were investigated. It was found that factor VIIa (10 nM) significantly increased interleukin-8 (IL-8) expression at the mRNA and protein levels, enhanced TF mRNA expression and TF activity, and decreased caspase-7 expression at the mRNA and protein levels in the SW620 cells. These effects of factor VIIa were similar to those of PAR2-AP. All effects of factor VIIa were blocked by anti-TF and anti-PAR2 antibodies, but not by an isotype control antibody. Furthermore, both PAR2-AP and factor VIIa decreased the phosphorylation of p38 mitogen-activated protein kinase (MAPK). The results of this study suggest that the TF/VIIa complex regulates IL-8, TF and caspase-7 expression in SW620 cells via PAR2 activation, thereby promoting colon cancer cell proliferation and migration. The p38MAPK signal transduction pathway may negatively regulate these processes.

[Investigation of the mechanisms of coagulation factor VIIa-induced colon cancer SW620 cell proliferation and migration].

OBJECTIVE: To investigate the mechanisms that coagulation factor VIIa promotes proliferation and migration of a colon cancer cell line (SW620 cells) in vitro. METHODS: The expression of interleukin 8 (IL-8), tissue factor (TF), caspase-7 and p-p38 MAPK in SW620 cells treated with factor VIIa or protease activated receptor 2 agonist (PAR2-AP) was measured by ELISA, Western-blotting and QT-PCR. RESULTS: Factor VIIa and PAR2-AP induced IL-8 expression at both mRNA and protein levels, upregulated TF mRNA expression and TF activity, but down-regulated caspase-7 mRNA and p-p38 MAPK levels in SW620 cells. The effects of factor VIIa were not only blocked by anti-TF but also by anti-PAR2 antibodies. CONCLUSION: Factor VIIa binds to TF on cell surface, forming a complex which activates PAR2, then provoking IL-8 and TF expression, and suppresses caspase-7 expression, thus promotes the tumor cell proliferation and migration. p38 MAPK may negatively regulate this process.

The expression and the functional roles of tissue factor and protease-activated receptor-2 on SW620 cells.

Tissue factor (TF) is believed to play an important role in tissue repair, inflammation, angiogenesis, and tumor metastasis. Protease-activated receptors (PARs) are widely expressed on various cells including tumor cells and associated with many pathological mechanisms. In the present study, the expression of TF and PAR1, PAR2 on human colon cancer cells (SW620 and SW480) was investigated and their functional roles on the behavior of tumor cells were evaluated. It was demonstrated that SW620 and SW480 cells expressed TF at antigen, activity and mRNA levels. However, the highly metastatic cell line SW620 showed slightly higher TF expression than the low metastatic cell line SW480. The PAR2 antigen was strongly expressed on the membrane of SW620 cells, but not on SW480 cells. The PAR1 antigen was not observed in SW620 or SW480 cells, while PAR1 and PAR2 mRNA was detected in SW620 and SW480 cells. The migratory potential of SW620 was stronger than that of SW480 seen in Boyden chambers. PAR2 agonist (SLIGKV-NH2) and factor VIIa significantly stimulated SW620 cell proliferation, migratory activity, and interleukin 8 (IL-8) secretion compared to control. The stimulating effects of factor VIIa could be inhibited by anti-TF and anti-PAR2 but not anti-PAR1 antibodies. In summary, this study demonstrates that TF and PAR2 are strongly expressed on highly metastatic colonic tumor cells and are closely associated with the proliferation and migration of the cells. TF may elucidate its roles in colonic cancer invasion and metastasis via PAR2 pathway.