A gadoxetic acid-enhanced MRI-based model using LI-RADS v2018 features for preoperatively predicting Ki-67 expression in hepatocellular carcinoma.

PURPOSE: To construct a gadoxetic acid-enhanced MRI (EOB-MRI) -based multivariable model to predict Ki-67 expression levels in hepatocellular carcinoma (HCC) using LI-RADS v2018 imaging features. METHODS: A total of 121 patients with HCC who underwent EOB-MRI were enrolled in this study. The patients were divided into three groups according to Ki-67 cut-offs: Ki-67 ≥ 20% (n = 86) vs. Ki-67 < 20% (n = 35); Ki-67 ≥ 30% (n = 73) vs. Ki-67 < 30% (n = 48); Ki-67 ≥ 50% (n = 45) vs. Ki-67 < 50% (n = 76). MRI features were analyzed to be associated with high Ki-67 expression using logistic regression to construct multivariable models. The performance characteristic of the models for the prediction of high Ki-67 expression was assessed using receiver operating characteristic curves. RESULTS: The presence of mosaic architecture (p = 0.045), the presence of infiltrative appearance (p = 0.039), and the absence of targetoid hepatobiliary phase (HBP, p = 0.035) were independent differential factors for the prediction of high Ki-67 status (≥ 50% vs. < 50%) in HCC patients, while no features could predict high Ki-67 status with thresholds of 20% (≥ 20% vs. < 20%) and 30% (≥ 30% vs. < 30%) (p > 0.05). Four models were constructed including model A (mosaic architecture and infiltrated appearance), model B (mosaic architecture and targetoid HBP), model C (infiltrated appearance and targetoid HBP), and model D (mosaic architecture, infiltrated appearance and targetoid HBP). The model D yielded better diagnostic performance than the model C (0.776 vs. 0.669, p = 0.002), but a comparable AUC than model A (0.776 vs. 0.781, p = 0.855) and model B (0.776 vs. 0.746, p = 0.076). CONCLUSIONS: Mosaic architecture, infiltrated appearance and targetoid HBP were sensitive imaging features for predicting Ki-67 index ≥ 50% and EOB-MRI model based on LI-RADS v2018 features may be an effective imaging approach for the risk stratification of patients with HCC before surgery.

MiR-3926 inhibits synovial fibroblasts proliferation and inflammatory cytokines secretion through targeting toll like receptor 5.

Rheumatoid arthritis synovial fibroblasts (RASFs) play a key role in the pathogenesis of rheumatoid arthritis (RA). This study was aimed to investigate the effects of miR-3926 on the biological activities of RASFs. The results showed that miR-3926 was significantly down-regulated in RASFs and RA synovial tissue. Overexpression of miR-3926 significantly inhibited RASFs proliferation and decreased the secretion of inflammatory cytokines including TNF-α, IL-1ß and IL-6 in RASFs. TLR5 was identified to be a direct target of miR-3926. TLR5 showed an opposite expression trends with miR-3926 in RASFs and RA synovial tissue. Overexpression of miR-3926 led to a reduction of endogenous TLR5 in RASFs, whereas down-regulation of miR-3926 increased TLR5 expression. Knocking down of TLR5 significantly inhibited RASFs proliferation and inflammatory cytokines secretion. Rescue experiments with a miR-3926-resistant variant of TLR5 showed that overexpression of TLR5 restored RASFs proliferation and inflammatory cytokines secretion in miR-3926-overexpressing RASFs. In conclusion, miR-3926 is downregulated in RA synovial tissues and its overexpression caused the inhibitory effects on RASF proliferation and inflammatory cytokines secretion by targeting TLR5. The miR-3926/TLR5 pathway may represent a novel target for prevention and treatment of RA.

Fractalkine stimulates cell growth and increases its expression via NF-κB pathway in RA-FLS.

BACKGROUND: After the onset of rheumatoid arthritis (RA), fibroblast-like synoviocytes (RA-FLS) which are specialized types of fibroblasts, become tumor-like, keeping their ability to increase proliferation and invasion. The mechanism of their tumor-like growth is unclear. Fractalkine (FKN), also called CX3CL1, plays an important role in the proliferation of cells. FKN may stimulate the proliferation of RA-FLS and the by nuclear factor κB (NF-κB) pathway may be one of the steps in this process. OBJECTIVE: To investigate whether FKN can stimulate cell growth and increase its expression in RA-FLS, and the relationship between the NF-κB pathway and the function of FKN. METHODS: FLS were isolated from primary synovial tissue obtained from three patients with RA who had undergone total joint replacement surgery or synovectomy in the Third Hospital Affiliated to Sun Yat-sen University from February 2009 to January 2010. FKN was used in different concentrations to stimulate RA-FLS with or without NF-κB pathway blocker (PDTC), and to test the proliferation of FLS after 24 h by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RA-FLS was treated with 100 ng/mL FKN or 100 µM PDTC for different periods, and messenger RNA (mRNA) expression of FKN and CX3CR1 in RA-FLS was detected by reverse transcription - polymerase chain reaction. We then tested the protein expression of NF-κBp65 in the cytoplasm and nucleus, respectively by Western blotting after treating the RA-FLS with 100 ng/mL FKN for different time periods. RESULTS: FKN stimulated cell growth in RA-FLS at the concentration of 50 or 100 ng/mL (P = 0.005 and P = 0.022, respectively). NF-κB pathway blocker inhibited FKN, promoting proliferation of RA-FLS. RA-FLS could express FKN and CX3CR1 mRNA in vitro. FKN up-regulated FKN expression after 18-h treatment (P = 0.012). PDTC disturbed the expression of FKN mRNA after 16-18 h treatment (P = 0.001 and P < 0.001, respectively). After stimulation with FKN for 1 h, the expression of NF-κBp65 in cytoplasm began to decrease (P = 0.010), and the expression of NF-κBp65 in the nucleus began to increase after 2 h (P = 0.011). CONCLUSION: These results suggest that FKN stimulates cells growth in RA-FLS and NF-κB pathway blocker inhibits FKN, promoting proliferation of RA-FLS. FKN induced activation of NF-κB activity. FKN up-regulates FKN mRNA expression in RA-FLS via the NF-κB pathway.